Variant 10-114204830-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_001395205.1(TDRD1):c.1234A>G(p.Ile412Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000613 in 1,599,030 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000063 ( 1 hom. )

Consequence

TDRD1
NM_001395205.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.87

Variant links:

Genes affected

TDRD1 (HGNC:11712): (tudor domain containing 1) This gene encodes a protein containing a tudor domain that is thought to function in the suppression of transposable elements during spermatogenesis. The related protein in mouse forms a complex with piRNAs and Piwi proteins to promote methylation and silencing of target sequences. This gene was observed to be upregulated by ETS transcription factor ERG in prostate tumors. [provided by RefSeq, Sep 2018]

TDRD1 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=0.036744475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDRD1	NM_001395205.1 linkuse as main transcript	c.1234A>G	p.Ile412Val	missense_variant	10/25	ENST00000695399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDRD1	ENST00000695399.1 linkuse as main transcript	c.1234A>G	p.Ile412Val	missense_variant	10/25		NM_001395205.1	P4	Q9BXT4-1
TDRD1	ENST00000251864.7 linkuse as main transcript	c.1234A>G	p.Ile412Val	missense_variant	10/26	1		A2	Q9BXT4-3
TDRD1	ENST00000369282.5 linkuse as main transcript	c.1234A>G	p.Ile412Val	missense_variant	10/25	5		A2
TDRD1	ENST00000369280.1 linkuse as main transcript	c.1234A>G	p.Ile412Val	missense_variant	10/24	5		A2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000478

GnomAD3 exomes

AF:

0.000114

AC:

AN:

237568

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

128338

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000623

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:

0.0000365

Gnomad OTH exome

AF:

0.000694

GnomAD4 exome

AF:

0.0000629

AC:

AN:

1446862

Hom.:

Cov.:

AF XY:

0.0000626

AC XY:

AN XY:

718598

show subpopulations

Gnomad4 AFR exome

AF:

0.0000608

Gnomad4 AMR exome

AF:

0.000599

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:

0.0000533

Gnomad4 OTH exome

AF:

0.0000834

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

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:

0.000478

Alfa

AF:

0.0000554

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.000140

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

Dec 21, 2022

The c.1234A>G (p.I412V) alteration is located in exon 10 (coding exon 9) of the TDRD1 gene. This alteration results from a A to G substitution at nucleotide position 1234, causing the isoleucine (I) at amino acid position 412 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

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.67

Cadd

Benign

9.9

Dann

Benign

0.43

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.63

T;T;T

M_CAP

Benign

0.0078

MetaRNN

Benign

0.037

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.17

N;N;N

REVEL

Benign

0.050

Sift

Benign

0.75

T;T;T

Sift4G

Benign

0.62

T;T;T

Polyphen

0.020

.;B;.

Vest4

0.18

MVP

0.26

MPC

0.46

ClinPred

0.026

GERP RS

3.7

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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