3-52525097-T-A

Variant summary

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

The NM_001134231.2(NT5DC2):​c.1213A>T​(p.Met405Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,477,808 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 0.000089 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

NT5DC2
NM_001134231.2 missense

Scores

3
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
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=0.2293311).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NT5DC2NM_001134231.2 linkuse as main transcriptc.1213A>T p.Met405Leu missense_variant 12/14 ENST00000422318.7
NT5DC2NM_022908.3 linkuse as main transcriptc.1102A>T p.Met368Leu missense_variant 12/14
NT5DC2XM_006713303.4 linkuse as main transcriptc.1213A>T p.Met405Leu missense_variant 12/14
NT5DC2XM_047448760.1 linkuse as main transcriptc.1102A>T p.Met368Leu missense_variant 12/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NT5DC2ENST00000422318.7 linkuse as main transcriptc.1213A>T p.Met405Leu missense_variant 12/145 NM_001134231.2 P2Q9H857-2

Frequencies

GnomAD3 genomes
AF:
0.0000889
AC:
12
AN:
135018
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000228
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000824
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000136
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000306
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000157
AC:
3
AN:
190704
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
104342
show subpopulations
Gnomad AFR exome
AF:
0.0000989
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:
0.0000590
Gnomad NFE exome
AF:
0.0000123
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000894
AC:
12
AN:
1342790
Hom.:
0
Cov.:
56
AF XY:
0.00000150
AC XY:
1
AN XY:
664480
show subpopulations
Gnomad4 AFR exome
AF:
0.0000334
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:
0.0000971
Gnomad4 NFE exome
AF:
0.00000576
Gnomad4 OTH exome
AF:
0.0000188
GnomAD4 genome
AF:
0.0000889
AC:
12
AN:
135018
Hom.:
0
Cov.:
32
AF XY:
0.000125
AC XY:
8
AN XY:
64250
show subpopulations
Gnomad4 AFR
AF:
0.000228
Gnomad4 AMR
AF:
0.0000824
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000136
Gnomad4 NFE
AF:
0.0000306
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000252
AC:
3

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 GeneticsDec 13, 2022The c.1213A>T (p.M405L) alteration is located in exon 12 (coding exon 12) of the NT5DC2 gene. This alteration results from a A to T substitution at nucleotide position 1213, causing the methionine (M) at amino acid position 405 to be replaced by a leucine (L). 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
0.64
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.22
CADD
Uncertain
25
DANN
Benign
0.97
DEOGEN2
Benign
0.029
T;T;.;.
Eigen
Benign
0.16
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.60
T;T;T;T
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.23
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.7
.;M;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-1.2
N;N;N;N
REVEL
Benign
0.22
Sift
Uncertain
0.021
D;D;D;D
Sift4G
Benign
0.095
T;T;T;T
Polyphen
0.080
.;B;.;.
Vest4
0.66, 0.65, 0.65
MutPred
0.44
.;Gain of relative solvent accessibility (P = 0.1259);.;.;
MVP
0.43
MPC
0.54
ClinPred
0.56
D
GERP RS
5.0
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6
Varity_R
0.54
gMVP
0.74

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: rs780544534; hg19: chr3-52559113; API