chr3-52524838-A-T

Variant summary

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

The NM_001134231.2(NT5DC2):​c.1391T>A​(p.Met464Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,612,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

NT5DC2
NM_001134231.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.70
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15823638).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NT5DC2NM_001134231.2 linkuse as main transcriptc.1391T>A p.Met464Lys missense_variant 13/14 ENST00000422318.7
NT5DC2NM_022908.3 linkuse as main transcriptc.1280T>A p.Met427Lys missense_variant 13/14
NT5DC2XM_006713303.4 linkuse as main transcriptc.1391T>A p.Met464Lys missense_variant 13/14
NT5DC2XM_047448760.1 linkuse as main transcriptc.1280T>A p.Met427Lys missense_variant 13/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NT5DC2ENST00000422318.7 linkuse as main transcriptc.1391T>A p.Met464Lys missense_variant 13/145 NM_001134231.2 P2Q9H857-2

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152032
Hom.:
0
Cov.:
33
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000123
AC:
3
AN:
244406
Hom.:
0
AF XY:
0.0000150
AC XY:
2
AN XY:
132922
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000278
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1460434
Hom.:
0
Cov.:
71
AF XY:
0.00000551
AC XY:
4
AN XY:
726496
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000809
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152032
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74258
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000312
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000825
AC:
1

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 GeneticsNov 18, 2022The c.1391T>A (p.M464K) alteration is located in exon 13 (coding exon 13) of the NT5DC2 gene. This alteration results from a T to A substitution at nucleotide position 1391, causing the methionine (M) at amino acid position 464 to be replaced by a lysine (K). 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
0.25
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
21
DANN
Benign
0.90
DEOGEN2
Benign
0.025
T;T;.;.
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.37
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.55
T;T;T;T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.16
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
.;L;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-2.2
N;N;N;N
REVEL
Benign
0.25
Sift
Benign
0.57
T;T;T;T
Sift4G
Benign
0.37
T;T;T;T
Polyphen
0.0010
.;B;.;.
Vest4
0.59, 0.60, 0.60
MutPred
0.48
.;Gain of ubiquitination at M427 (P = 0.023);.;.;
MVP
0.22
MPC
0.63
ClinPred
0.15
T
GERP RS
2.6
Varity_R
0.47
gMVP
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs144568381; hg19: chr3-52558854; API