1-212807766-A-G

Variant names:

• chr1-212807766-A-G
• rs1662629040
• NM_001042552.3:c.518A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001042552.3(TATDN3):​c.518A>G​(p.Asp173Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,396 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TATDN3 NM_001042552.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.68

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TATDN3	NM_001042552.3	c.518A>G	p.Asp173Gly	missense_variant	Exon 8 of 10	ENST00000366974.9	NP_001036017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TATDN3	ENST00000366974.9	c.518A>G	p.Asp173Gly	missense_variant	Exon 8 of 10	1	NM_001042552.3	ENSP00000355941.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461396 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727012

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.518A>G (p.D173G) alteration is located in exon 8 (coding exon 8) of the TATDN3 gene. This alteration results from a A to G substitution at nucleotide position 518, causing the aspartic acid (D) at amino acid position 173 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	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	25
DANN	Benign	0.92
DEOGEN2	Benign	0.061	.;T;.;.;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D;D
M_CAP	Benign	0.0061	T
MetaRNN	Uncertain	0.71	D;D;D;D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.74	N;N;.;N;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.4	D;D;D;D;D
REVEL	Pathogenic	0.65
Sift	Benign	0.10	T;T;T;T;T
Sift4G	Benign	0.13	T;T;T;T;T
Polyphen		0.20, 0.10	.;B;.;.;B
Vest4		0.90
MutPred		0.54		Gain of methylation at R175 (P = 0.0836);Gain of methylation at R175 (P = 0.0836);.;Gain of methylation at R175 (P = 0.0836);Gain of methylation at R175 (P = 0.0836);
MVP		0.28
MPC		0.37
ClinPred		0.97	D
GERP RS		5.8
Varity_R		0.70
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs1662629040; hg19: chr1-212981108;