Variant 3-52525090-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001134231.2(NT5DC2):c.1220G>A(p.Arg407Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000454 in 1,433,010 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

NT5DC2
NM_001134231.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.06

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NT5DC2	NM_001134231.2 link	c.1220G>A	p.Arg407Gln	missense_variant	12/14	ENST00000422318.7	NP_001127703.1	Q9H857-2
NT5DC2	NM_022908.3 link	c.1109G>A	p.Arg370Gln	missense_variant	12/14		NP_075059.1	Q9H857-1
NT5DC2	XM_006713303.4 link	c.1220G>A	p.Arg407Gln	missense_variant	12/14		XP_006713366.1
NT5DC2	XM_047448760.1 link	c.1109G>A	p.Arg370Gln	missense_variant	12/14		XP_047304716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NT5DC2	ENST00000422318.7 link	c.1220G>A	p.Arg407Gln	missense_variant	12/14	5	NM_001134231.2	ENSP00000406933.2		Q9H857-2

Frequencies

GnomAD3 genomes

AF:

0.0000139

AC:

AN:

143882

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000305

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000152

AC:

AN:

196786

Hom.:

AF XY:

0.00

AC XY:

AN XY:

107814

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000672

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000118

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000489

AC:

AN:

1289128

Hom.:

Cov.:

AF XY:

0.0000408

AC XY:

AN XY:

637416

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000829

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000794

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000518

Gnomad4 OTH exome

AF:

0.0000801

GnomAD4 genome

AF:

0.0000139

AC:

AN:

143882

Hom.:

Cov.:

AF XY:

0.0000287

AC XY:

AN XY:

69806

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000305

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000227

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

Dec 03, 2024

The c.1220G>A (p.R407Q) 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 1220, causing the arginine (R) at amino acid position 407 to be replaced by a glutamine (Q). 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

Uncertain

0.40

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.021

T;T;.;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.057

MetaRNN

Uncertain

0.54

D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

.;M;.;.

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.055

T;D;D;D

Sift4G

Benign

0.16

T;T;T;T

Polyphen

0.51

.;P;.;.

Vest4

0.85, 0.84, 0.81

MVP

0.47

MPC

1.2

ClinPred

0.87

GERP RS

5.0

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.37

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.20

Position offset: -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