Variant 19-32757068-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001366102.1(TDRD12):c.803C>T(p.Ser268Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000322 in 1,551,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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: 0.0000029 ( 0 hom. )

Consequence

TDRD12
NM_001366102.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47

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:

Genome browser will be placed here

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=0.26719618).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRD12	NM_001366102.1 linkuse as main transcript	c.803C>T	p.Ser268Phe	missense_variant	8/33	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.803C>T	p.Ser268Phe	missense_variant	8/33	5	NM_001366102.1	ENSP00000492643	A2
TDRD12	ENST00000444215.6 linkuse as main transcript	c.803C>T	p.Ser268Phe	missense_variant	8/28	1		ENSP00000416248		Q587J7-1
TDRD12	ENST00000647536.1 linkuse as main transcript	c.803C>T	p.Ser268Phe	missense_variant	8/33			ENSP00000496698	P4
TDRD12	ENST00000421545.2 linkuse as main transcript	c.803C>T	p.Ser268Phe	missense_variant	8/13	5		ENSP00000390621		Q587J7-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152158

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

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1399576

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690296

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:

0.00000371

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74330

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

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

Dec 26, 2023

The c.803C>T (p.S268F) alteration is located in exon 8 (coding exon 8) of the TDRD12 gene. This alteration results from a C to T substitution at nucleotide position 803, causing the serine (S) at amino acid position 268 to be replaced by a phenylalanine (F). 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

0.10

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0053

T;.;.

Eigen

Benign

0.073

Eigen_PC

Benign

0.024

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.95

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.7

N;.;N

REVEL

Benign

0.14

Sift

Uncertain

0.0040

D;.;D

Sift4G

Uncertain

0.0050

D;.;D

Polyphen

0.99

D;.;.

Vest4

0.42

MutPred

0.40

Loss of disorder (P = 0.0351);Loss of disorder (P = 0.0351);Loss of disorder (P = 0.0351);

MVP

0.17

ClinPred

0.97

GERP RS

3.3

Varity_R

0.12

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