3-10249276-C-T

Variant names:

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

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>T​(p.Leu26Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L26V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TATDN2 NM_014760.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.20575991).

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>T	p.Leu26Phe	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>T	p.Leu26Phe	missense	Exon 2 of 8	ENSP00000408736.2	Q93075
	TATDN2	ENST00000287652.8	TSL:1	c.76C>T	p.Leu26Phe	missense	Exon 2 of 8	ENSP00000287652.4	Q93075
	ENSG00000289763	ENST00000699225.1		c.108C>T	p.Ala36Ala	synonymous	Exon 2 of 2	ENSP00000514219.1	A0A8V8TPP0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436664 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 712036

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: 0.00 AC: 0 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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0048	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.5
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.052
Sift	Benign	0.13	T
Sift4G	Benign	0.17	T
Polyphen		0.95	P
Vest4		0.32
MutPred		0.14		Loss of catalytic residue at L26 (P = 0.0079)
MVP		0.40
MPC		0.54
ClinPred		0.93	D
GERP RS		3.5
Varity_R		0.14
gMVP		0.11
Mutation Taster		=97/3	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;