rs1662629040

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042552.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TATDN3	NM_001042552.3	MANE Select	c.518A>G	p.Asp173Gly	missense	Exon 8 of 10	NP_001036017.1	Q17R31-1
	TATDN3	NM_001146171.2		c.518A>G	p.Asp173Gly	missense	Exon 8 of 10	NP_001139643.1	Q17R31-3
	TATDN3	NM_001042553.3		c.518A>G	p.Asp173Gly	missense	Exon 8 of 10	NP_001036018.1	Q17R31-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TATDN3	ENST00000366974.9	TSL:1 MANE Select	c.518A>G	p.Asp173Gly	missense	Exon 8 of 10	ENSP00000355941.4	Q17R31-1
	TATDN3	ENST00000366973.8	TSL:1	c.518A>G	p.Asp173Gly	missense	Exon 8 of 10	ENSP00000355940.4	Q17R31-2
	TATDN3	ENST00000531963.5	TSL:1	c.518A>G	p.Asp173Gly	missense	Exon 8 of 10	ENSP00000433755.1	Q17R31-5

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

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111836

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0061	T
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.74	N
PhyloP100		8.7
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Pathogenic	0.65
Sift	Benign	0.10	T
Sift4G	Benign	0.13	T
Polyphen		0.20	B
Vest4		0.90
MutPred		0.54		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
Mutation Taster		=8/92	disease causing

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

Other links and lift over

dbSNP: rs1662629040; hg19: chr1-212981108;