Variant 3-10249510-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014760.4(TATDN2):c.310C>G(p.Arg104Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,609,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

TATDN2
NM_014760.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.207

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0645453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TATDN2	NM_014760.4 link	c.310C>G	p.Arg104Gly	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.310C>G	p.Arg104Gly	missense_variant	2/8	1	NM_014760.4	ENSP00000408736.2	Q93075
TATDN2	ENST00000287652.8 link	c.310C>G	p.Arg104Gly	missense_variant	2/8	1		ENSP00000287652.4	Q93075
ENSG00000272410	ENST00000437082.5 link	n.139C>G		non_coding_transcript_exon_variant	1/8	2		ENSP00000402783.1	H7C1W4
ENSG00000272410	ENST00000450534.1 link	n.139C>G		non_coding_transcript_exon_variant	1/8	2		ENSP00000399689.1	H7C1D0

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

243568

Hom.:

AF XY:

0.0000227

AC XY:

AN XY:

132416

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000166

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000912

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000618

AC:

AN:

1457032

Hom.:

Cov.:

AF XY:

0.00000966

AC XY:

AN XY:

724780

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000451

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 30, 2024

The c.310C>G (p.R104G) alteration is located in exon 2 (coding exon 1) of the TATDN2 gene. This alteration results from a C to G substitution at nucleotide position 310, causing the arginine (R) at amino acid position 104 to be replaced by a glycine (G). 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

0.080

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0052

T;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.67

.;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.065

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.93

N;N

REVEL

Benign

0.028

Sift

Benign

0.072

T;T

Sift4G

Benign

0.10

T;T

Polyphen

0.14

B;B

Vest4

0.25

MutPred

0.29

Loss of MoRF binding (P = 0.0076);Loss of MoRF binding (P = 0.0076);

MVP

0.32

MPC

0.33

ClinPred

0.074

GERP RS

1.3

Varity_R

0.084

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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