NM_014760.4:c.76C>G

Variant names:

• chr3-10249276-C-G
• rs775955627
• NM_014760.4:c.76C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014760.4(TATDN2):​c.76C>G​(p.Leu26Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,436,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TATDN2 NM_014760.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.47
• Publications: 0 publications found

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]

ENSG00000289763 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10214645).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014760.4. 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
	TATDN2	NM_014760.4	MANE Select	c.76C>G	p.Leu26Val	missense	Exon 2 of 8	NP_055575.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TATDN2	ENST00000448281.7	TSL:1 MANE Select	c.76C>G	p.Leu26Val	missense	Exon 2 of 8	ENSP00000408736.2	Q93075
	TATDN2	ENST00000287652.8	TSL:1	c.76C>G	p.Leu26Val	missense	Exon 2 of 8	ENSP00000287652.4	Q93075
	ENSG00000289763	ENST00000699225.1		c.108C>G	p.Ala36Ala	synonymous	Exon 2 of 2	ENSP00000514219.1	A0A8V8TPP0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000850 AC: 2 AN: 235222 AF XY: 0.0000157

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000114

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1436664 Hom.: 0 Cov.: 31 AF XY: 0.00000281 AC XY: 2 AN XY: 712036

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32652

American (AMR) AF: 0.00 AC: 0 AN: 41110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24700

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39202

South Asian (SAS) AF: 0.00 AC: 0 AN: 84032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5630

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1097704

Other (OTH) AF: 0.00 AC: 0 AN: 59112

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions as Germline

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	Benign	0.076
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.017
Eigen_PC	Benign	0.057
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.5
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.032
Sift	Benign	0.15	T
Sift4G	Benign	0.37	T
Polyphen		0.46	P
Vest4		0.30
MutPred		0.15		Gain of MoRF binding (P = 0.0797)
MVP		0.32
MPC		0.28
ClinPred		0.22	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.12
gMVP		0.13
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs775955627; hg19: chr3-10290960;