Genetic Variant TATDN3:p.Gly182Glu (chr1-212807793-G-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001042552.3(TATDN3):c.545G>A(p.Gly182Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

TATDN3
NM_001042552.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.31

Variant links:

Genes affected

TATDN3 (HGNC:27010): (TatD DNase domain containing 3) 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 nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TATDN3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.882

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TATDN3	NM_001042552.3 link	c.545G>A	p.Gly182Glu	missense_variant	Exon 8 of 10	ENST00000366974.9	NP_001036017.1	Q17R31-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TATDN3	ENST00000366974.9 link	c.545G>A	p.Gly182Glu	missense_variant	Exon 8 of 10	1	NM_001042552.3	ENSP00000355941.4		Q17R31-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152122

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:

0.000192

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:

0.00000398

AC:

AN:

251168

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727138

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.00202

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

Jul 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.545G>A (p.G182E) alteration is located in exon 8 (coding exon 8) of the TATDN3 gene. This alteration results from a G to A substitution at nucleotide position 545, causing the glycine (G) at amino acid position 182 to be replaced by a glutamic acid (E). 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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.47

BayesDel_noAF

Pathogenic

0.44

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

.;T;.;.;.

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

D;D;D;D;D

M_CAP

Benign

0.021

MetaRNN

Pathogenic

0.88

D;D;D;D;D

MetaSVM

Uncertain

-0.21

MutationAssessor

Pathogenic

3.3

M;M;.;M;M

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-6.4

D;D;D;D;D

REVEL

Uncertain

0.56

Sift

Uncertain

0.0030

D;D;D;D;D

Sift4G

Benign

0.25

T;T;D;T;T

Polyphen

0.99, 0.97

.;D;.;.;D

Vest4

0.93

MutPred

0.71

Loss of catalytic residue at V183 (P = 0.0571);Loss of catalytic residue at V183 (P = 0.0571);.;Loss of catalytic residue at V183 (P = 0.0571);Loss of catalytic residue at V183 (P = 0.0571);

MVP

0.28

MPC

0.70

ClinPred

0.99

GERP RS

4.8

Varity_R

0.97

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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