Variant chr8-494507-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 ENST00000324079.11(TDRP):c.199C>A(p.Pro67Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,613,684 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

TDRP
ENST00000324079.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.38

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:

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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
TDRP	NM_001384899.1 linkuse as main transcript	c.199C>A	p.Pro67Thr	missense_variant	2/3	ENST00000324079.11	NP_001371828.1
TDRP	NM_001256113.2 linkuse as main transcript	c.199C>A	p.Pro67Thr	missense_variant	2/4		NP_001243042.1
TDRP	NM_175075.5 linkuse as main transcript	c.199C>A	p.Pro67Thr	missense_variant	3/4		NP_778250.2
TDRP	XM_047421392.1 linkuse as main transcript	c.229C>A	p.Pro77Thr	missense_variant	3/4		XP_047277348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRP	ENST00000324079.11 linkuse as main transcript	c.199C>A	p.Pro67Thr	missense_variant	2/3	1	NM_001384899.1	ENSP00000315111	P1	Q86YL5-1
TDRP	ENST00000523656.5 linkuse as main transcript	c.199C>A	p.Pro67Thr	missense_variant	3/5	5		ENSP00000430325		Q86YL5-2
TDRP	ENST00000524229.1 linkuse as main transcript	n.130C>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152136

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

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249196

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135192

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461548

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727062

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:

0.0000144

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74308

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:

0.0000434

Hom.:

Bravo

AF:

0.00000756

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 05, 2022

The c.199C>A (p.P67T) alteration is located in exon 2 (coding exon 2) of the TDRP gene. This alteration results from a C to A substitution at nucleotide position 199, causing the proline (P) at amino acid position 67 to be replaced by a threonine (T). 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

0.13

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

.;T;T;.

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.79

T;T;.;.

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.63

D;D;D;D

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

2.0

M;M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-6.7

D;.;D;D

REVEL

Uncertain

0.49

Sift

Uncertain

0.0050

D;.;D;D

Sift4G

Uncertain

0.0060

D;D;D;D

Polyphen

1.0

.;D;D;.

Vest4

0.87

MutPred

0.19

Loss of glycosylation at P67 (P = 0.0148);Loss of glycosylation at P67 (P = 0.0148);Loss of glycosylation at P67 (P = 0.0148);Loss of glycosylation at P67 (P = 0.0148);

MVP

0.076

MPC

0.0050

ClinPred

0.95

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.41

gMVP

0.21

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