Variant chr8-492558-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001384899.1(TDRP):c.399G>T(p.Trp133Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000868 in 1,612,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

TDRP
NM_001384899.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78

Variant links:

Genes affected

TDRP (HGNC:26951): (testis development related protein) Acts upstream of or within spermatogenesis. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TDRP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27652848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRP	NM_001384899.1 linkuse as main transcript	c.399G>T	p.Trp133Cys	missense_variant	3/3	ENST00000324079.11	NP_001371828.1
TDRP	NM_001256113.2 linkuse as main transcript	c.399G>T	p.Trp133Cys	missense_variant	3/4		NP_001243042.1	Q86YL5-2
TDRP	NM_175075.5 linkuse as main transcript	c.399G>T	p.Trp133Cys	missense_variant	4/4		NP_778250.2	Q86YL5-1
TDRP	XM_047421392.1 linkuse as main transcript	c.429G>T	p.Trp143Cys	missense_variant	4/4		XP_047277348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRP	ENST00000324079.11 linkuse as main transcript	c.399G>T	p.Trp133Cys	missense_variant	3/3	1	NM_001384899.1	ENSP00000315111.6		Q86YL5-1
TDRP	ENST00000523656.5 linkuse as main transcript	c.399G>T	p.Trp133Cys	missense_variant	4/5	5		ENSP00000430325.1		Q86YL5-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1460632

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726532

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:

0.0000108

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.00000828

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

Nov 24, 2024

The c.399G>T (p.W133C) alteration is located in exon 3 (coding exon 3) of the TDRP gene. This alteration results from a G to T substitution at nucleotide position 399, causing the tryptophan (W) at amino acid position 133 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

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.20

.;T;T;.

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.66

T;T;.;.

M_CAP

Benign

0.017

MetaRNN

Benign

0.28

T;T;T;T

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.9

L;L;L;L

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-7.5

D;.;D;D

REVEL

Benign

0.21

Sift

Uncertain

0.0040

D;.;D;D

Sift4G

Uncertain

0.044

D;T;T;D

Polyphen

0.99

.;D;D;.

Vest4

0.57

MutPred

0.33

Gain of glycosylation at S132 (P = 0.0233);Gain of glycosylation at S132 (P = 0.0233);Gain of glycosylation at S132 (P = 0.0233);Gain of glycosylation at S132 (P = 0.0233);

MVP

0.11

MPC

0.0055

ClinPred

0.93

GERP RS

5.2

Varity_R

0.44

gMVP

0.10

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