3-10270255-C-T

Position:

• chr3-10270255-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014760.4(TATDN2):​c.1073C>T​(p.Pro358Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,613,958 control chromosomes in the GnomAD database, including 12,145 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.15 (2110 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10035 hom.)
• Consequence: TATDN2 NM_014760.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.966

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]

ENSG00000272410 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004538268).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TATDN2	NM_014760.4	c.1073C>T	p.Pro358Leu	missense_variant	4/8	ENST00000448281.7	NP_055575.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TATDN2	ENST00000448281.7	c.1073C>T	p.Pro358Leu	missense_variant	4/8	1	NM_014760.4	ENSP00000408736.2
ENSG00000272410	ENST00000437082.5	n.902C>T		non_coding_transcript_exon_variant	3/8	2		ENSP00000402783.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22845 AN: 151960 Hom.: 2099 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0976

Gnomad OTH AF: 0.136

GnomAD3 exomes AF: 0.123 AC: 30912 AN: 251446 Hom.: 2395 AF XY: 0.121 AC XY: 16458 AN XY: 135902

Gnomad AFR exome AF: 0.253

Gnomad AMR exome AF: 0.0641

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.259

Gnomad SAS exome AF: 0.114

Gnomad FIN exome AF: 0.138

Gnomad NFE exome AF: 0.0973

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.108 AC: 157652 AN: 1461880 Hom.: 10035 Cov.: 33 AF XY: 0.108 AC XY: 78492 AN XY: 727242

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.0695

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.0952

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.150 AC: 22877 AN: 152078 Hom.: 2110 Cov.: 32 AF XY: 0.152 AC XY: 11294 AN XY: 74348

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.0976

Gnomad4 OTH AF: 0.136

Alfa AF: 0.109 Hom.: 2196

Bravo AF: 0.150

TwinsUK AF: 0.102 AC: 379

ALSPAC AF: 0.0947 AC: 365

ESP6500AA AF: 0.246 AC: 1083

ESP6500EA AF: 0.0957 AC: 823

ExAC AF: 0.125 AC: 15211

Asia WGS AF: 0.186 AC: 649 AN: 3478

EpiCase AF: 0.0960

EpiControl AF: 0.103

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.67
DEOGEN2	Benign	0.0025	T;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.55	.;T
MetaRNN	Benign	0.0045	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.079
Sift	Benign	0.037	D;D
Sift4G	Benign	0.28	T;T
Polyphen		0.15	B;B
Vest4		0.052
MPC		0.19
ClinPred		0.036	T
GERP RS		4.7
Varity_R		0.051
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2075352; hg19: chr3-10311939; COSMIC: COSV55051570; COSMIC: COSV55051570;