Variant 10-114204185-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001395205.1(TDRD1):c.1094T>C(p.Leu365Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,445,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TDRD1
NM_001395205.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.32

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_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.988

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDRD1	NM_001395205.1 linkuse as main transcript	c.1094T>C	p.Leu365Pro	missense_variant	9/25	ENST00000695399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TDRD1	ENST00000695399.1 linkuse as main transcript	c.1094T>C	p.Leu365Pro	missense_variant	9/25		NM_001395205.1	P4	Q9BXT4-1
TDRD1	ENST00000251864.7 linkuse as main transcript	c.1094T>C	p.Leu365Pro	missense_variant	9/26	1		A2	Q9BXT4-3
TDRD1	ENST00000369282.5 linkuse as main transcript	c.1094T>C	p.Leu365Pro	missense_variant	9/25	5		A2
TDRD1	ENST00000369280.1 linkuse as main transcript	c.1094T>C	p.Leu365Pro	missense_variant	9/24	5		A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000427

AC:

AN:

234248

Hom.:

AF XY:

0.00000789

AC XY:

AN XY:

126750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000575

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:

6.92e-7

AC:

AN:

1445644

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718866

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

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

Cov.:

ExAC

AF:

0.00000824

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

Jan 02, 2024

The c.1094T>C (p.L365P) alteration is located in exon 9 (coding exon 8) of the TDRD1 gene. This alteration results from a T to C substitution at nucleotide position 1094, causing the leucine (L) at amino acid position 365 to be replaced by a proline (P). 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

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.060

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.68

T;T;T

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.99

D;D;D

MetaSVM

Benign

-0.99

MutationTaster

Benign

0.96

D;D;D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-5.9

D;D;D

REVEL

Uncertain

0.51

Sift

Uncertain

0.0010

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.92

MutPred

0.91

Loss of stability (P = 0.034);Loss of stability (P = 0.034);Loss of stability (P = 0.034);

MVP

0.78

MPC

0.97

ClinPred

0.96

GERP RS

6.1

gMVP

0.93

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