Variant 19-32748510-T-C 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.475T>C(p.Tyr159His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000357 in 1,399,506 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

TDRD12
NM_001366102.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.99

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.475T>C	p.Tyr159His	missense_variant	5/33	ENST00000639142.2	NP_001353031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRD12	ENST00000639142.2 linkuse as main transcript	c.475T>C	p.Tyr159His	missense_variant	5/33	5	NM_001366102.1	ENSP00000492643	A2
TDRD12	ENST00000444215.6 linkuse as main transcript	c.475T>C	p.Tyr159His	missense_variant	5/28	1		ENSP00000416248		Q587J7-1
TDRD12	ENST00000647536.1 linkuse as main transcript	c.475T>C	p.Tyr159His	missense_variant	5/33			ENSP00000496698	P4
TDRD12	ENST00000421545.2 linkuse as main transcript	c.475T>C	p.Tyr159His	missense_variant	5/13	5		ENSP00000390621		Q587J7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000357

AC:

AN:

1399506

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

690264

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

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:

0.0000516

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

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

Apr 06, 2022

The c.475T>C (p.Y159H) alteration is located in exon 5 (coding exon 5) of the TDRD12 gene. This alteration results from a T to C substitution at nucleotide position 475, causing the tyrosine (Y) at amino acid position 159 to be replaced by a histidine (H). 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

T;.;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.81

T;T;T

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.52

D;D;D

MetaSVM

Benign

-0.73

MutationTaster

Benign

0.92

D;D

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.9

D;.;D

REVEL

Uncertain

0.32

Sift

Pathogenic

0.0

D;.;D

Sift4G

Pathogenic

0.0

D;.;D

Polyphen

1.0

D;.;.

Vest4

0.38

MutPred

0.62

Gain of catalytic residue at I157 (P = 0.075);Gain of catalytic residue at I157 (P = 0.075);Gain of catalytic residue at I157 (P = 0.075);

MVP

0.081

ClinPred

0.99

GERP RS

5.3

Varity_R

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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