Variant 3-52525048-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001134231.2(NT5DC2):c.1262G>A(p.Arg421His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,599,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

NT5DC2
NM_001134231.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15

Variant links:

Genes affected

NT5DC2 (HGNC:25717): (5'-nucleotidase domain containing 2) Predicted to enable 5'-nucleotidase activity. Predicted to be involved in dephosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

NT5DC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15350336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NT5DC2	NM_001134231.2 linkuse as main transcript	c.1262G>A	p.Arg421His	missense_variant	12/14	ENST00000422318.7
NT5DC2	NM_022908.3 linkuse as main transcript	c.1151G>A	p.Arg384His	missense_variant	12/14
NT5DC2	XM_006713303.4 linkuse as main transcript	c.1262G>A	p.Arg421His	missense_variant	12/14
NT5DC2	XM_047448760.1 linkuse as main transcript	c.1151G>A	p.Arg384His	missense_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NT5DC2	ENST00000422318.7 linkuse as main transcript	c.1262G>A	p.Arg421His	missense_variant	12/14	5	NM_001134231.2	P2	Q9H857-2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000276

AC:

AN:

217122

Hom.:

AF XY:

0.0000336

AC XY:

AN XY:

118966

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000107

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000210

Gnomad OTH exome

AF:

0.000184

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1447680

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

719106

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000467

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.0000828

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000362

Gnomad4 OTH exome

AF:

0.0000502

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000718

ExAC

AF:

0.0000167

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2023

The c.1262G>A (p.R421H) alteration is located in exon 12 (coding exon 12) of the NT5DC2 gene. This alteration results from a G to A substitution at nucleotide position 1262, causing the arginine (R) at amino acid position 421 to be replaced by a histidine (H). 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

Benign

0.086

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.54

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

T;T;.;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.29

.;N;.;.

MutationTaster

Benign

0.87

N;N;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.070

N;N;N;N

REVEL

Benign

0.022

Sift

Benign

0.33

T;T;T;T

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.085

.;B;.;.

Vest4

0.37, 0.37, 0.39

MutPred

0.41

.;Gain of helix (P = 0.0199);.;.;

MVP

0.42

MPC

0.43

ClinPred

0.053

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.064

gMVP

0.57

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over