chr3-52527332-G-A

Variant summary

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

The NM_001134231.2(NT5DC2):​c.1081C>T​(p.Arg361Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000217 in 1,614,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

NT5DC2
NM_001134231.2 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.64
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=0.17579526).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NT5DC2NM_001134231.2 linkuse as main transcriptc.1081C>T p.Arg361Trp missense_variant 10/14 ENST00000422318.7
NT5DC2NM_022908.3 linkuse as main transcriptc.970C>T p.Arg324Trp missense_variant 10/14
NT5DC2XM_006713303.4 linkuse as main transcriptc.1081C>T p.Arg361Trp missense_variant 10/14
NT5DC2XM_047448760.1 linkuse as main transcriptc.970C>T p.Arg324Trp missense_variant 10/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NT5DC2ENST00000422318.7 linkuse as main transcriptc.1081C>T p.Arg361Trp missense_variant 10/145 NM_001134231.2 P2Q9H857-2

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152192
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00115
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:
0.0000598
AC:
15
AN:
250990
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135854
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000707
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000192
AC:
28
AN:
1461804
Hom.:
0
Cov.:
31
AF XY:
0.0000206
AC XY:
15
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000403
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.00000629
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152310
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000642
ExAC
AF:
0.0000494
AC:
6

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 GeneticsMay 31, 2023The c.1081C>T (p.R361W) alteration is located in exon 10 (coding exon 10) of the NT5DC2 gene. This alteration results from a C to T substitution at nucleotide position 1081, causing the arginine (R) at amino acid position 361 to be replaced by a tryptophan (W). 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
0.49
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.31
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.084
T;T;.;.
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.86
D;D;D;D
M_CAP
Benign
0.056
D
MetaRNN
Benign
0.18
T;T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.2
.;M;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Pathogenic
-5.2
D;D;D;D
REVEL
Benign
0.24
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
0.50, 0.51, 0.48
MVP
0.60
MPC
1.1
ClinPred
0.80
D
GERP RS
4.3
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.7
Varity_R
0.48
gMVP
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs200789146; hg19: chr3-52561348; API