chr3-52525085-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001134231.2(NT5DC2):​c.1225G>T​(p.Gly409Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,581,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

NT5DC2
NM_001134231.2 missense

Scores

12
4
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.79
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 Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.956

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NT5DC2NM_001134231.2 linkuse as main transcriptc.1225G>T p.Gly409Cys missense_variant 12/14 ENST00000422318.7
NT5DC2NM_022908.3 linkuse as main transcriptc.1114G>T p.Gly372Cys missense_variant 12/14
NT5DC2XM_006713303.4 linkuse as main transcriptc.1225G>T p.Gly409Cys missense_variant 12/14
NT5DC2XM_047448760.1 linkuse as main transcriptc.1114G>T p.Gly372Cys missense_variant 12/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NT5DC2ENST00000422318.7 linkuse as main transcriptc.1225G>T p.Gly409Cys missense_variant 12/145 NM_001134231.2 P2Q9H857-2

Frequencies

GnomAD3 genomes
AF:
0.000121
AC:
18
AN:
149258
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000248
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00107
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:
0.000486
GnomAD3 exomes
AF:
0.0000199
AC:
4
AN:
200616
Hom.:
0
AF XY:
0.0000364
AC XY:
4
AN XY:
110004
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000332
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:
0.0000347
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000838
AC:
12
AN:
1431888
Hom.:
0
Cov.:
57
AF XY:
0.00000845
AC XY:
6
AN XY:
710152
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000122
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:
0.00000547
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
AF:
0.000121
AC:
18
AN:
149344
Hom.:
0
Cov.:
32
AF XY:
0.0000686
AC XY:
5
AN XY:
72848
show subpopulations
Gnomad4 AFR
AF:
0.0000247
Gnomad4 AMR
AF:
0.00107
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:
0.000481
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.000181
ExAC
AF:
0.0000419
AC:
5

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 16, 2023The c.1225G>T (p.G409C) alteration is located in exon 12 (coding exon 12) of the NT5DC2 gene. This alteration results from a G to T substitution at nucleotide position 1225, causing the glycine (G) at amino acid position 409 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
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Pathogenic
0.17
CADD
Pathogenic
34
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T;T;.;.
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
1.0
D;D;D;D
M_CAP
Pathogenic
0.42
D
MetaRNN
Pathogenic
0.96
D;D;D;D
MetaSVM
Benign
-0.52
T
MutationAssessor
Pathogenic
3.5
.;M;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.88
D
PROVEAN
Pathogenic
-8.7
D;D;D;D
REVEL
Pathogenic
0.67
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
0.94, 0.95, 0.94
MutPred
0.85
.;Gain of catalytic residue at W373 (P = 0.0475);.;.;
MVP
0.72
MPC
1.1
ClinPred
0.99
D
GERP RS
4.2
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.0
Varity_R
0.87
gMVP
0.96

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.32
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.32
Position offset: -13

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: rs747318346; hg19: chr3-52559101; API