Variant chr8-544679-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.79C>T(p.Pro27Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000402 in 1,244,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

TDRP
NM_001384899.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.338

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 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=0.04786384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRP	NM_001384899.1 linkuse as main transcript	c.79C>T	p.Pro27Ser	missense_variant	1/3	ENST00000324079.11	NP_001371828.1
TDRP	NM_001256113.2 linkuse as main transcript	c.79C>T	p.Pro27Ser	missense_variant	1/4		NP_001243042.1	Q86YL5-2
TDRP	NM_175075.5 linkuse as main transcript	c.79C>T	p.Pro27Ser	missense_variant	2/4		NP_778250.2	Q86YL5-1
TDRP	XM_047421392.1 linkuse as main transcript	c.-28900C>T		5_prime_UTR_variant	1/4		XP_047277348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRP	ENST00000324079.11 linkuse as main transcript	c.79C>T	p.Pro27Ser	missense_variant	1/3	1	NM_001384899.1	ENSP00000315111.6		Q86YL5-1
TDRP	ENST00000523656.5 linkuse as main transcript	c.79C>T	p.Pro27Ser	missense_variant	2/5	5		ENSP00000430325.1		Q86YL5-2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151866

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:

0.000196

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000366

AC:

AN:

1092928

Hom.:

Cov.:

AF XY:

0.00000385

AC XY:

AN XY:

519946

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:

0.0000446

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000216

Gnomad4 OTH exome

AF:

0.0000227

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151866

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Jun 06, 2023

The c.79C>T (p.P27S) alteration is located in exon 1 (coding exon 1) of the TDRP gene. This alteration results from a C to T substitution at nucleotide position 79, causing the proline (P) at amino acid position 27 to be replaced by a serine (S). 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

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.58

DEOGEN2

Benign

0.0082

.;T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.41

T;T;.;.

M_CAP

Benign

0.019

MetaRNN

Benign

0.048

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N;N;N

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.44

N;.;N;N

REVEL

Benign

0.054

Sift

Benign

0.66

T;.;T;T

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.15

.;B;B;.

Vest4

0.22

MutPred

0.21

Gain of phosphorylation at P27 (P = 0.029);Gain of phosphorylation at P27 (P = 0.029);Gain of phosphorylation at P27 (P = 0.029);Gain of phosphorylation at P27 (P = 0.029);

MVP

0.072

MPC

0.0029

ClinPred

0.028

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.026

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