Variant 1-154547433-T-C 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.977T>C(p.Val326Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000162 in 1,614,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

TDRD10
NM_182499.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0440

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:

TDRD10 (HGNC:):

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=0.006552011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRD10	NM_182499.4 linkuse as main transcript	c.977T>C	p.Val326Ala	missense_variant	12/13	ENST00000368482.8	NP_872305.3	Q5VZ19-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TDRD10	ENST00000368482.8 linkuse as main transcript	c.977T>C	p.Val326Ala	missense_variant	12/13	1	NM_182499.4	ENSP00000357467.4	Q5VZ19-2
TDRD10	ENST00000479937.5 linkuse as main transcript	n.722T>C		non_coding_transcript_exon_variant	7/8	1
TDRD10	ENST00000368480.3 linkuse as main transcript	c.977T>C	p.Val326Ala	missense_variant	12/12	2		ENSP00000357465.3	Q5VZ19-1
TDRD10	ENST00000468714.5 linkuse as main transcript	n.526T>C		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00548

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:

0.000478

GnomAD3 exomes

AF:

0.000386

AC:

AN:

251270

Hom.:

AF XY:

0.000412

AC XY:

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00655

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000161

AC:

235

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

125

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00647

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000171

AC:

AN:

152362

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000829

Hom.:

Bravo

AF:

0.000170

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000280

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000415

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

Oct 18, 2021

The c.977T>C (p.V326A) alteration is located in exon 12 (coding exon 11) of the TDRD10 gene. This alteration results from a T to C substitution at nucleotide position 977, causing the valine (V) at amino acid position 326 to be replaced by an alanine (A). 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

Benign

0.20

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.0039

.;T

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.0066

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;L

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.44

N;N

REVEL

Benign

0.021

Sift

Uncertain

0.0080

D;D

Polyphen

0.83

P;P

Vest4

0.27

MVP

0.12

MPC

0.50

ClinPred

0.030

GERP RS

2.6

Varity_R

0.048

gMVP

0.64

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