Variant chr3-101565275-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_017819.4(TRMT10C):c.494T>A(p.Leu165Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00037 in 1,612,164 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

TRMT10C
NM_017819.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.49

Variant links:

Genes affected

TRMT10C (HGNC:26022): (tRNA methyltransferase 10C, mitochondrial RNase P subunit) This gene encodes the precursor of a subunit of the mitochondrial ribonuclease P, which is involved in 5' processing of mitochondrial tRNAs. The encoded protein may confer RNA-binding capacity to mitochondrial ribonuclease P and may be essential for transcript processing, RNA modification, translation and mitochondrial respiration. [provided by RefSeq, Nov 2012]

TRMT10C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.004102677).

BP6

Variant 3-101565275-T-A is Benign according to our data. Variant chr3-101565275-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 737603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT10C	NM_017819.4 linkuse as main transcript	c.494T>A	p.Leu165Gln	missense_variant	2/2	ENST00000309922.7	NP_060289.2	Q7L0Y3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT10C	ENST00000309922.7 linkuse as main transcript	c.494T>A	p.Leu165Gln	missense_variant	2/2	1	NM_017819.4	ENSP00000312356.6		Q7L0Y3
TRMT10C	ENST00000495642.1 linkuse as main transcript	c.494T>A	p.Leu165Gln	missense_variant	2/2	3		ENSP00000419389.1		C9JVB6

Frequencies

GnomAD3 genomes

AF:

0.00207

AC:

315

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

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:

0.0000735

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000536

AC:

133

AN:

247964

Hom.:

AF XY:

0.000438

AC XY:

AN XY:

134732

show subpopulations

Gnomad AFR exome

AF:

0.00753

Gnomad AMR exome

AF:

0.000440

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000193

AC:

282

AN:

1459898

Hom.:

Cov.:

AF XY:

0.000156

AC XY:

113

AN XY:

726132

show subpopulations

Gnomad4 AFR exome

AF:

0.00673

Gnomad4 AMR exome

AF:

0.000495

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.00207

AC:

315

AN:

152266

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00698

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000277

Hom.:

Bravo

AF:

0.00245

ESP6500AA

AF:

0.00826

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000712

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 11, 2022	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.25

DEOGEN2

Benign

0.0024

T;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.41

T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

0.85

N;N

REVEL

Benign

0.056

Sift

Benign

0.55

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.013

B;.

Vest4

0.12

MVP

0.24

MPC

0.17

ClinPred

0.0049

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.81

Varity_R

0.070

gMVP

0.20

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