Variant 6-46688382-G-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_001010870.3(TDRD6):c.254G>A(p.Arg85His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TDRD6
NM_001010870.3 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 4.28

Variant links:

Genes affected

TDRD6 (HGNC:21339): (tudor domain containing 6) This gene encodes a tudor domain-containing protein and component of the chromatoid body, a type of ribonucleoprotein granule present in male germ cells. Studies in rodents have demonstrated a role for the encoded protein in spermiogenesis and the nonsense mediated decay (NMD) pathway. This protein is a major autoantigen in human patients with autoimmune polyendocrine syndrome type 1 (APS1). [provided by RefSeq, Oct 2016]

TDRD6 links:

TDRD6 (HGNC:):

TDRD6 links:

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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=0.37694055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRD6	NM_001010870.3 linkuse as main transcript	c.254G>A	p.Arg85His	missense_variant	1/4	ENST00000316081.11	NP_001010870.1	O60522-1
TDRD6	NM_001168359.2 linkuse as main transcript	c.254G>A	p.Arg85His	missense_variant	1/3		NP_001161831.1	O60522-2
TDRD6	NR_144468.2 linkuse as main transcript	n.1372+6743G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRD6	ENST00000316081.11 linkuse as main transcript	c.254G>A	p.Arg85His	missense_variant	1/4	1	NM_001010870.3	ENSP00000346065.5		O60522-1
TDRD6	ENST00000544460.5 linkuse as main transcript	c.254G>A	p.Arg85His	missense_variant	1/3	2		ENSP00000443299.1		O60522-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1383388

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

682822

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TDRD6-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 30, 2024

The TDRD6 c.254G>A variant is predicted to result in the amino acid substitution p.Arg85His. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.0010

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.32

.;T

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.076

MetaRNN

Benign

0.38

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.22

Sift

Benign

0.076

T;T

Sift4G

Uncertain

0.045

D;D

Polyphen

1.0

.;D

Vest4

0.47

MVP

0.41

MPC

0.25

ClinPred

0.98

GERP RS

5.3

Varity_R

0.097

gMVP

0.64

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