rs771561899

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001134665.3(TRMT10A):c.899G>A(p.Gly300Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,614,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G300R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

TRMT10A
NM_001134665.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.296

Publications

0 publications found

Variant links:

Genes affected

TRMT10A (HGNC:28403): (tRNA methyltransferase 10A) This gene encodes a protein that belongs to the tRNA (Guanine-1)-methyltransferase family. A similar gene in yeast modifies several different tRNA species. Mutations in this gene are associated with microcephaly, short stature, and impaired glucose metabolism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

TRMT10A Gene-Disease associations (from GenCC):

microcephaly, short stature, and impaired glucose metabolism 1
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
primary microcephaly-mild intellectual disability-young-onset diabetes syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TRMT10A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0202142).

BP6

Variant 4-99549209-C-T is Benign according to our data. Variant chr4-99549209-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1441812. Variant chr4-99549209-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1441812. Variant chr4-99549209-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1441812. Variant chr4-99549209-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1441812. Variant chr4-99549209-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1441812. Variant chr4-99549209-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1441812. Variant chr4-99549209-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1441812. Variant chr4-99549209-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1441812. Variant chr4-99549209-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1441812. Variant chr4-99549209-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1441812. Variant chr4-99549209-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1441812. Variant chr4-99549209-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 1441812.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT10A	NM_001134665.3 link	c.899G>A	p.Gly300Asp	missense_variant	Exon 8 of 8	ENST00000394876.7	NP_001128137.1	Q8TBZ6V9HVY8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRMT10A	ENST00000394876.7 link	c.899G>A	p.Gly300Asp	missense_variant	Exon 8 of 8	1	NM_001134665.3	ENSP00000378342.2	Q8TBZ6
TRMT10A	ENST00000273962.7 link	c.899G>A	p.Gly300Asp	missense_variant	Exon 8 of 8	1		ENSP00000273962.3	Q8TBZ6
TRMT10A	ENST00000394877.7 link	c.899G>A	p.Gly300Asp	missense_variant	Exon 8 of 8	2		ENSP00000378343.3	Q8TBZ6

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000796

AC:

AN:

251356

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.000335

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111980

Other (OTH)

AF:

0.0000497

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41438

American (AMR)

AF:

0.000131

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Oct 24, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 300 of the TRMT10A protein (p.Gly300Asp). This variant is present in population databases (rs771561899, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with TRMT10A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1441812). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Inborn genetic diseases

Benign:1

May 25, 2025

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.59

(source)

DANN

Benign

0.29

DEOGEN2

Benign

0.0035

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.34

.;.;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.020

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

N;N;N

PhyloP100

-0.30

PrimateAI

Benign

0.23

PROVEAN

Benign

0.73

N;N;N

REVEL

Benign

0.047

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.18

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.041

MutPred

0.15

Gain of glycosylation at S302 (P = 0.0054);Gain of glycosylation at S302 (P = 0.0054);Gain of glycosylation at S302 (P = 0.0054);

MVP

0.040

MPC

0.19

ClinPred

0.017

GERP RS

-3.0

Varity_R

0.081

gMVP

0.066

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over