4-99558191-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001134665.3(TRMT10A):c.206G>A(p.Arg69His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00246 in 1,596,038 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 6 hom. )

Consequence

TRMT10A
NM_001134665.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.94

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00686568).

BP6

Variant 4-99558191-C-T is Benign according to our data. Variant chr4-99558191-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 437058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00264 (401/152114) while in subpopulation NFE AF= 0.00348 (236/67896). AF 95% confidence interval is 0.00311. There are 5 homozygotes in gnomad4. There are 228 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT10A	NM_001134665.3 link	c.206G>A	p.Arg69His	missense_variant	Exon 3 of 8	ENST00000394876.7	NP_001128137.1	Q8TBZ6V9HVY8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT10A	ENST00000394876.7 link	c.206G>A	p.Arg69His	missense_variant	Exon 3 of 8	1	NM_001134665.3	ENSP00000378342.2		Q8TBZ6

Frequencies

GnomAD3 genomes

AF:

0.00263

AC:

400

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0115

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00348

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00257

AC:

600

AN:

233286

Hom.:

AF XY:

0.00268

AC XY:

337

AN XY:

125934

show subpopulations

Gnomad AFR exome

AF:

0.000379

Gnomad AMR exome

AF:

0.000437

Gnomad ASJ exome

AF:

0.00134

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000192

Gnomad FIN exome

AF:

0.00974

Gnomad NFE exome

AF:

0.00316

Gnomad OTH exome

AF:

0.00248

GnomAD4 exome

AF:

0.00244

AC:

3523

AN:

1443924

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

1745

AN XY:

717820

show subpopulations

Gnomad4 AFR exome

AF:

0.000375

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.00182

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000390

Gnomad4 FIN exome

AF:

0.00866

Gnomad4 NFE exome

AF:

0.00253

Gnomad4 OTH exome

AF:

0.00242

GnomAD4 genome

AF:

0.00264

AC:

401

AN:

152114

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

228

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0115

Gnomad4 NFE

AF:

0.00348

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00273

Hom.:

Bravo

AF:

0.00153

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00266

AC:

323

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TRMT10A: BS2 -

not specified

Benign:1

May 03, 2017

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

TRMT10A-related disorder

Benign:1

Sep 06, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.090

T;T;T;T;T

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.85

.;.;T;D;T

MetaRNN

Benign

0.0069

T;T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.4

M;M;M;.;.

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-2.7

D;D;D;D;D

REVEL

Benign

0.19

Sift

Benign

0.17

T;T;T;T;T

Sift4G

Benign

0.064

T;T;T;.;.

Polyphen

0.080

B;B;B;.;.

Vest4

0.34

MVP

0.60

MPC

0.19

ClinPred

0.034

GERP RS

5.8

Varity_R

0.33

gMVP

0.10

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over