Variant chr8-492415-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001384899.1(TDRP):c.542C>T(p.Pro181Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,557,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

TDRP
NM_001384899.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.655

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049389392).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TDRP	NM_001384899.1 linkuse as main transcript	c.542C>T	p.Pro181Leu	missense_variant	3/3	ENST00000324079.11	NP_001371828.1
TDRP	NM_175075.5 linkuse as main transcript	c.542C>T	p.Pro181Leu	missense_variant	4/4		NP_778250.2
TDRP	XM_047421392.1 linkuse as main transcript	c.572C>T	p.Pro191Leu	missense_variant	4/4		XP_047277348.1
TDRP	NM_001256113.2 linkuse as main transcript	c.498+44C>T		intron_variant			NP_001243042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRP	ENST00000324079.11 linkuse as main transcript	c.542C>T	p.Pro181Leu	missense_variant	3/3	1	NM_001384899.1	ENSP00000315111	P1	Q86YL5-1
TDRP	ENST00000523656.5 linkuse as main transcript	c.498+44C>T		intron_variant		5		ENSP00000430325		Q86YL5-2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000477

AC:

AN:

209432

Hom.:

AF XY:

0.0000621

AC XY:

AN XY:

112758

show subpopulations

Gnomad AFR exome

AF:

0.0000740

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000921

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000619

Gnomad OTH exome

AF:

0.000200

GnomAD4 exome

AF:

0.0000377

AC:

AN:

1405394

Hom.:

Cov.:

AF XY:

0.0000376

AC XY:

AN XY:

691216

show subpopulations

Gnomad4 AFR exome

AF:

0.0000310

Gnomad4 AMR exome

AF:

0.0000506

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000389

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000417

Gnomad4 OTH exome

AF:

0.0000346

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000120

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000331

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

Jun 22, 2021

The c.542C>T (p.P181L) alteration is located in exon 3 (coding exon 3) of the TDRP gene. This alteration results from a C to T substitution at nucleotide position 542, causing the proline (P) at amino acid position 181 to be replaced by a leucine (L). 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

0.081

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.59

T;.

M_CAP

Benign

0.0085

MetaRNN

Benign

0.049

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

D;D;N

PROVEAN

Benign

0.17

.;N

REVEL

Benign

0.039

Sift

Benign

0.18

.;T

Sift4G

Uncertain

0.055

T;T

Polyphen

0.053

B;B

Vest4

0.24

MVP

0.040

ClinPred

0.016

GERP RS

1.1

Varity_R

0.018

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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