Variant 10-114203559-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001395205.1(TDRD1):c.973G>A(p.Val325Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000811 in 1,603,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TDRD1
NM_001395205.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.562

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24266878).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDRD1	NM_001395205.1 linkuse as main transcript	c.973G>A	p.Val325Ile	missense_variant	8/25	ENST00000695399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDRD1	ENST00000695399.1 linkuse as main transcript	c.973G>A	p.Val325Ile	missense_variant	8/25		NM_001395205.1	P4	Q9BXT4-1
TDRD1	ENST00000251864.7 linkuse as main transcript	c.973G>A	p.Val325Ile	missense_variant	8/26	1		A2	Q9BXT4-3
TDRD1	ENST00000369282.5 linkuse as main transcript	c.973G>A	p.Val325Ile	missense_variant	8/25	5		A2
TDRD1	ENST00000369280.1 linkuse as main transcript	c.973G>A	p.Val325Ile	missense_variant	8/24	5		A2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000417

AC:

AN:

240016

Hom.:

AF XY:

0.00000769

AC XY:

AN XY:

129998

show subpopulations

Gnomad AFR exome

AF:

0.0000625

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000345

AC:

AN:

1451126

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721866

show subpopulations

Gnomad4 AFR exome

AF:

0.000153

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

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

Jun 22, 2021

The c.973G>A (p.V325I) alteration is located in exon 8 (coding exon 7) of the TDRD1 gene. This alteration results from a G to A substitution at nucleotide position 973, causing the valine (V) at amino acid position 325 to be replaced by an isoleucine (I). 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

-0.37

BayesDel_noAF

Benign

-0.59

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-0.88

MutationTaster

Benign

0.85

N;N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.46

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.21

T;T;T

Sift4G

Uncertain

0.024

D;D;D

Polyphen

0.87

.;P;.

Vest4

0.17

MutPred

0.56

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.51

MPC

0.61

ClinPred

0.73

GERP RS

4.9

gMVP

0.16

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