Variant 1-154544387-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182499.4(TDRD10):c.667A>G(p.Met223Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000478 in 1,589,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

TDRD10
NM_182499.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66

Variant links:

Genes affected

TDRD10 (HGNC:25316): (tudor domain containing 10) Predicted to enable RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

TDRD10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059827447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDRD10	NM_182499.4 linkuse as main transcript	c.667A>G	p.Met223Val	missense_variant	10/13	ENST00000368482.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDRD10	ENST00000368482.8 linkuse as main transcript	c.667A>G	p.Met223Val	missense_variant	10/13	1	NM_182499.4	P1	Q5VZ19-2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000385

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

GnomAD3 exomes

AF:

0.0000962

AC:

AN:

207936

Hom.:

AF XY:

0.0000990

AC XY:

AN XY:

111108

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000354

Gnomad ASJ exome

AF:

0.00120

Gnomad EAS exome

AF:

0.000129

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000435

Gnomad OTH exome

AF:

0.000375

GnomAD4 exome

AF:

0.0000473

AC:

AN:

1436766

Hom.:

Cov.:

AF XY:

0.0000604

AC XY:

AN XY:

711970

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000256

Gnomad4 ASJ exome

AF:

0.00141

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000164

Gnomad4 OTH exome

AF:

0.000201

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000225

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000909

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2022

The c.667A>G (p.M223V) alteration is located in exon 10 (coding exon 9) of the TDRD10 gene. This alteration results from a A to G substitution at nucleotide position 667, causing the methionine (M) at amino acid position 223 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.59

Cadd

Benign

Dann

Uncertain

0.98

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.97

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.54

N;N

REVEL

Benign

0.085

Sift

Pathogenic

0.0

D;D

Polyphen

0.050

B;B

Vest4

0.62

MVP

0.095

MPC

0.96

ClinPred

0.072

GERP RS

-0.12

Varity_R

0.47

gMVP

0.78

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