3-52524475-G-A

Variant summary

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

The NM_001134231.2(NT5DC2):​c.1669C>T​(p.Arg557Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,612,658 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

NT5DC2
NM_001134231.2 missense

Scores

3
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.56
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]
STAB1 (HGNC:18628): (stabilin 1) This gene encodes a large, transmembrane receptor protein which may function in angiogenesis, lymphocyte homing, cell adhesion, or receptor scavenging. The protein contains 7 fasciclin, 16 epidermal growth factor (EGF)-like, and 2 laminin-type EGF-like domains as well as a C-type lectin-like hyaluronan-binding Link module. The protein is primarily expressed on sinusoidal endothelial cells of liver, spleen, and lymph node. The receptor has been shown to endocytose ligands such as low density lipoprotein, Gram-positive and Gram-negative bacteria, and advanced glycosylation end products. Supporting its possible role as a scavenger receptor, the protein rapidly cycles between the plasma membrane and early endosomes. [provided by RefSeq, Jul 2008]

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.1669C>T p.Arg557Cys missense_variant 14/14 ENST00000422318.7
STAB1NM_015136.3 linkuse as main transcriptc.*119G>A 3_prime_UTR_variant 69/69 ENST00000321725.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NT5DC2ENST00000422318.7 linkuse as main transcriptc.1669C>T p.Arg557Cys missense_variant 14/145 NM_001134231.2 P2Q9H857-2
STAB1ENST00000321725.10 linkuse as main transcriptc.*119G>A 3_prime_UTR_variant 69/691 NM_015136.3 P1Q9NY15-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152224
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1460434
Hom.:
0
Cov.:
70
AF XY:
0.00000551
AC XY:
4
AN XY:
726500
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00000719
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152224
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000315
Hom.:
0
Bravo
AF:
0.00000378

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 23, 2024The c.1669C>T (p.R557C) alteration is located in exon 14 (coding exon 14) of the NT5DC2 gene. This alteration results from a C to T substitution at nucleotide position 1669, causing the arginine (R) at amino acid position 557 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
Uncertain
0.49
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.080
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.032
T;T;.;.
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.96
D;D;D;D
M_CAP
Benign
0.060
D
MetaRNN
Uncertain
0.60
D;D;D;D
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
1.9
.;M;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.73
T
PROVEAN
Uncertain
-3.1
D;D;D;D
REVEL
Uncertain
0.34
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
0.88, 0.88, 0.89
MutPred
0.46
.;Loss of solvent accessibility (P = 1e-04);.;.;
MVP
0.63
MPC
1.3
ClinPred
0.99
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.52
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs898260470; hg19: chr3-52558491; COSMIC: COSV58736491; COSMIC: COSV58736491; API