Variant 10-114203388-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001395205.1(TDRD1):c.802G>T(p.Gly268Cys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000139 in 1,437,396 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TDRD1
NM_001395205.1 missense, splice_region

Scores

Splicing: ADA: 0.9999

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.55

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRD1	NM_001395205.1 linkuse as main transcript	c.802G>T	p.Gly268Cys	missense_variant, splice_region_variant	8/25	ENST00000695399.1	NP_001382134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TDRD1	ENST00000695399.1 linkuse as main transcript	c.802G>T	p.Gly268Cys	missense_variant, splice_region_variant	8/25		NM_001395205.1	ENSP00000511878.1	Q9BXT4-1
TDRD1	ENST00000251864.7 linkuse as main transcript	c.802G>T	p.Gly268Cys	missense_variant, splice_region_variant	8/26	1		ENSP00000251864.2	Q9BXT4-3
TDRD1	ENST00000369282.5 linkuse as main transcript	c.802G>T	p.Gly268Cys	missense_variant, splice_region_variant	8/25	5		ENSP00000358288.1	H9KV63
TDRD1	ENST00000369280.1 linkuse as main transcript	c.802G>T	p.Gly268Cys	missense_variant, splice_region_variant	8/24	5		ENSP00000358286.1	H9KV62

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1437396

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713866

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000338

GnomAD4 genome

Cov.:

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 17, 2023

The c.802G>T (p.G268C) alteration is located in exon 8 (coding exon 7) of the TDRD1 gene. This alteration results from a G to T substitution at nucleotide position 802, causing the glycine (G) at amino acid position 268 to be replaced by a cysteine (C). 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

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.74

D;D;D

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.2

.;M;.

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0070

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.77

MutPred

0.52

Gain of methylation at K267 (P = 0.0158);Gain of methylation at K267 (P = 0.0158);Gain of methylation at K267 (P = 0.0158);

MVP

0.39

MPC

0.79

ClinPred

0.99

GERP RS

5.6

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.99

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over