Variant chr3-10249451-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014760.4(TATDN2):c.251T>C(p.Phe84Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 1,613,352 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

TATDN2
NM_014760.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.321

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:

ENSG00000272410 (HGNC:):

ENSG00000272410 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0030035377).

BP6

Variant 3-10249451-T-C is Benign according to our data. Variant chr3-10249451-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3453233.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TATDN2	NM_014760.4 link	c.251T>C	p.Phe84Ser	missense_variant	2/8	ENST00000448281.7	NP_055575.3	Q93075A0A024R2F3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TATDN2	ENST00000448281.7 link	c.251T>C	p.Phe84Ser	missense_variant	2/8	1	NM_014760.4	ENSP00000408736.2	Q93075
TATDN2	ENST00000287652.8 link	c.251T>C	p.Phe84Ser	missense_variant	2/8	1		ENSP00000287652.4	Q93075
ENSG00000272410	ENST00000437082.5 link	n.80T>C		non_coding_transcript_exon_variant	1/8	2		ENSP00000402783.1	H7C1W4
ENSG00000272410	ENST00000450534.1 link	n.80T>C		non_coding_transcript_exon_variant	1/8	2		ENSP00000399689.1	H7C1D0

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000241

AC:

AN:

248792

Hom.:

AF XY:

0.000274

AC XY:

AN XY:

135202

show subpopulations

Gnomad AFR exome

AF:

0.0000653

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.000555

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000285

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000157

AC:

229

AN:

1461106

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

135

AN XY:

726854

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000614

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.000135

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000388

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000223

Hom.:

Bravo

AF:

0.000484

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.000305

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000534

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.96

DANN

Benign

0.54

DEOGEN2

Benign

0.0021

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0038

LIST_S2

Benign

0.16

.;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.0

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

0.82

N;N

REVEL

Benign

0.011

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.16

MVP

0.19

MPC

0.33

ClinPred

0.021

GERP RS

-1.1

Varity_R

0.039

gMVP

0.13

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