3-52525274-G-A

Variant summary

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

The NM_001134231.2(NT5DC2):​c.1141C>T​(p.Arg381Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,612,682 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

NT5DC2
NM_001134231.2 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02
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]

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 UniProt
NT5DC2NM_001134231.2 linkuse as main transcriptc.1141C>T p.Arg381Cys missense_variant 11/14 ENST00000422318.7
NT5DC2NM_022908.3 linkuse as main transcriptc.1030C>T p.Arg344Cys missense_variant 11/14
NT5DC2XM_006713303.4 linkuse as main transcriptc.1141C>T p.Arg381Cys missense_variant 11/14
NT5DC2XM_047448760.1 linkuse as main transcriptc.1030C>T p.Arg344Cys missense_variant 11/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NT5DC2ENST00000422318.7 linkuse as main transcriptc.1141C>T p.Arg381Cys missense_variant 11/145 NM_001134231.2 P2Q9H857-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152184
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
249214
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135270
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000581
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000890
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1460498
Hom.:
0
Cov.:
32
AF XY:
0.0000151
AC XY:
11
AN XY:
726520
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000448
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152184
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000264
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsJun 22, 2023The c.1141C>T (p.R381C) alteration is located in exon 11 (coding exon 11) of the NT5DC2 gene. This alteration results from a C to T substitution at nucleotide position 1141, causing the arginine (R) at amino acid position 381 to be replaced by a cysteine (C). 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
0.33
BayesDel_addAF
Benign
-0.089
T
BayesDel_noAF
Benign
-0.19
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.088
T;T;.;.
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Benign
0.66
D
LIST_S2
Uncertain
0.86
D;T;D;T
M_CAP
Benign
0.074
D
MetaRNN
Uncertain
0.56
D;D;D;D
MetaSVM
Benign
-0.94
T
MutationAssessor
Uncertain
2.9
.;M;.;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Uncertain
0.75
T
PROVEAN
Pathogenic
-5.4
D;D;D;D
REVEL
Benign
0.17
Sift
Uncertain
0.0020
D;D;D;D
Sift4G
Uncertain
0.0080
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
0.67, 0.66, 0.61
MutPred
0.50
.;Loss of MoRF binding (P = 0.0362);.;.;
MVP
0.59
MPC
0.58
ClinPred
0.98
D
GERP RS
4.2
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.1
Varity_R
0.47
gMVP
0.75

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.

Other links and lift over

dbSNP: rs750636981; hg19: chr3-52559290; COSMIC: COSV58741225; COSMIC: COSV58741225; API