Variant chr19-32748501-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 NM_001366102.1(TDRD12):c.466G>T(p.Ala156Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000193 in 1,551,704 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

TDRD12
NM_001366102.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.61

Variant links:

Genes affected

TDRD12 (HGNC:25044): (tudor domain containing 12) Predicted to enable ATP binding activity; RNA helicase activity; and nucleic acid binding activity. Predicted to be involved in several processes, including gamete generation; gene silencing by RNA; and piRNA metabolic process. Predicted to be part of PET complex. [provided by Alliance of Genome Resources, Apr 2022]

TDRD12 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	UniProt
TDRD12	NM_001366102.1 linkuse as main transcript	c.466G>T	p.Ala156Ser	missense_variant	5/33	ENST00000639142.2	NP_001353031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TDRD12	ENST00000639142.2 linkuse as main transcript	c.466G>T	p.Ala156Ser	missense_variant	5/33	5	NM_001366102.1	ENSP00000492643.2	A0A1W2PRK2
TDRD12	ENST00000444215.6 linkuse as main transcript	c.466G>T	p.Ala156Ser	missense_variant	5/28	1		ENSP00000416248.2	Q587J7-1
TDRD12	ENST00000647536.1 linkuse as main transcript	c.466G>T	p.Ala156Ser	missense_variant	5/33			ENSP00000496698.1	A0A2R8Y872
TDRD12	ENST00000421545.2 linkuse as main transcript	c.466G>T	p.Ala156Ser	missense_variant	5/13	5		ENSP00000390621.2	Q587J7-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152228

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:

0.00

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

GnomAD4 exome

AF:

0.0000193

AC:

AN:

1399476

Hom.:

Cov.:

AF XY:

0.0000188

AC XY:

AN XY:

690252

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:

0.0000250

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.0000282

Hom.:

Bravo

AF:

0.00000378

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

Nov 22, 2023

The c.466G>T (p.A156S) alteration is located in exon 5 (coding exon 5) of the TDRD12 gene. This alteration results from a G to T substitution at nucleotide position 466, causing the alanine (A) at amino acid position 156 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

0.23

BayesDel_addAF

Benign

0.0026

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0044

T;.;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Benign

0.067

MetaRNN

Uncertain

0.65

D;D;D

MetaSVM

Benign

-0.30

MutationTaster

Benign

0.96

D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.9

N;.;D

REVEL

Benign

0.28

Sift

Pathogenic

0.0

D;.;D

Sift4G

Uncertain

0.025

D;.;D

Polyphen

1.0

D;.;.

Vest4

0.51

MutPred

0.63

Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);

MVP

0.18

ClinPred

1.0

GERP RS

5.3

Varity_R

0.36

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