Variant chr8-492562-G-C 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_001384899.1(TDRP):c.395C>G(p.Ser132Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

TDRP
NM_001384899.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14854196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TDRP	NM_001384899.1 linkuse as main transcript	c.395C>G	p.Ser132Cys	missense_variant	3/3	ENST00000324079.11	NP_001371828.1
TDRP	NM_001256113.2 linkuse as main transcript	c.395C>G	p.Ser132Cys	missense_variant	3/4		NP_001243042.1
TDRP	NM_175075.5 linkuse as main transcript	c.395C>G	p.Ser132Cys	missense_variant	4/4		NP_778250.2
TDRP	XM_047421392.1 linkuse as main transcript	c.425C>G	p.Ser142Cys	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.395C>G	p.Ser132Cys	missense_variant	3/3	1	NM_001384899.1	ENSP00000315111	P1	Q86YL5-1
TDRP	ENST00000523656.5 linkuse as main transcript	c.395C>G	p.Ser132Cys	missense_variant	4/5	5		ENSP00000430325		Q86YL5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000815

AC:

AN:

245306

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133392

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000113

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:

0.00000274

AC:

AN:

1460830

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726652

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

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

May 17, 2023

The c.395C>G (p.S132C) alteration is located in exon 3 (coding exon 3) of the TDRP gene. This alteration results from a C to G substitution at nucleotide position 395, causing the serine (S) at amino acid position 132 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

Benign

0.084

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

.;T;T;.

Eigen

Benign

0.046

Eigen_PC

Benign

-0.079

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.39

T;T;.;.

M_CAP

Benign

0.0086

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.6

L;L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.5

D;.;D;D

REVEL

Benign

0.13

Sift

Benign

0.057

T;.;T;T

Sift4G

Uncertain

0.030

D;D;D;D

Polyphen

1.0

.;D;D;.

Vest4

0.26

MutPred

0.23

Gain of catalytic residue at S132 (P = 0.0276);Gain of catalytic residue at S132 (P = 0.0276);Gain of catalytic residue at S132 (P = 0.0276);Gain of catalytic residue at S132 (P = 0.0276);

MVP

0.16

MPC

0.0030

ClinPred

0.34

GERP RS

3.3

Varity_R

0.11

gMVP

0.038

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