Variant 3-10249399-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000448281.7(TATDN2):c.199C>T(p.Arg67Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000693 in 1,612,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00073 ( 0 hom. )

Consequence

TATDN2
ENST00000448281.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.774

Variant links:

Genes affected

TATDN2 (HGNC:28988): (TatD DNase domain containing 2) Predicted to enable metal ion binding activity and nuclease activity. Predicted to be involved in nucleic acid phosphodiester bond hydrolysis. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TATDN2 links:

(HGNC:):

links:

Genome browser will be placed here

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=0.060938418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TATDN2	NM_014760.4 linkuse as main transcript	c.199C>T	p.Arg67Trp	missense_variant	2/8	ENST00000448281.7	NP_055575.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TATDN2	ENST00000448281.7 linkuse as main transcript	c.199C>T	p.Arg67Trp	missense_variant	2/8	1	NM_014760.4	ENSP00000408736	P1
TATDN2	ENST00000287652.8 linkuse as main transcript	c.199C>T	p.Arg67Trp	missense_variant	2/8	1		ENSP00000287652	P1
	ENST00000699225.1 linkuse as main transcript			downstream_gene_variant				ENSP00000514219	P1

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000603

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000356

AC:

AN:

247036

Hom.:

AF XY:

0.000305

AC XY:

AN XY:

134278

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000464

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000605

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.000732

AC:

1069

AN:

1460650

Hom.:

Cov.:

AF XY:

0.000687

AC XY:

499

AN XY:

726660

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000493

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000908

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000315

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000163

Hom.:

Bravo

AF:

0.000412

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000593

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

Jul 26, 2022

The c.199C>T (p.R67W) alteration is located in exon 2 (coding exon 1) of the TATDN2 gene. This alteration results from a C to T substitution at nucleotide position 199, causing the arginine (R) at amino acid position 67 to be replaced by a tryptophan (W). 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

0.11

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0026

T;T

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.76

.;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.10

N;N

REVEL

Benign

0.057

Sift

Uncertain

0.028

D;D

Sift4G

Uncertain

0.033

D;D

Polyphen

0.96

D;D

Vest4

0.27

MVP

0.51

MPC

0.37

ClinPred

0.079

GERP RS

1.8

Varity_R

0.083

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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