chr2-18563896-C-T

Variant summary

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

The NM_033253.4(NT5C1B):​c.1553G>A​(p.Arg518Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R518W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

NT5C1B
NM_033253.4 missense

Scores

1
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.32
Variant links:
Genes affected
NT5C1B (HGNC:17818): (5'-nucleotidase, cytosolic IB) Cytosolic 5-prime nucleotidases, such as NT5C1B, catalyze production of adenosine, which regulates diverse physiologic processes (Sala-Newby and Newby, 2001 [PubMed 11690631]).[supplied by OMIM, Mar 2008]
NT5C1B-RDH14 (HGNC:38831): (NT5C1B-RDH14 readthrough) This locus represents naturally occurring read-through transcription between the neighboring NT5C1B (5'-nucleotidase, cytosolic IB) and RDH14 (retinol dehydrogenase 14) genes on chromosome 2. Alternative splicing results in multiple transcript variants, one of which encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Nov 2010]

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 rank MANE Protein UniProt
NT5C1BNM_033253.4 linkc.1553G>A p.Arg518Gln missense_variant Exon 9 of 9 ENST00000304081.9 NP_150278.2 Q96P26-2B3KUK6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NT5C1BENST00000304081.9 linkc.1553G>A p.Arg518Gln missense_variant Exon 9 of 9 1 NM_033253.4 ENSP00000305979.4 Q96P26-2
NT5C1B-RDH14ENST00000532967.5 linkc.1733G>A p.Arg578Gln missense_variant Exon 10 of 11 2 ENSP00000433415.1
NT5C1BENST00000406971.6 linkn.*874G>A non_coding_transcript_exon_variant Exon 10 of 10 5 ENSP00000383905.2 C4AM88
NT5C1BENST00000406971.6 linkn.*874G>A 3_prime_UTR_variant Exon 10 of 10 5 ENSP00000383905.2 C4AM88

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152100
Hom.:
0
Cov.:
32
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:
0.00000398
AC:
1
AN:
251432
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135890
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461858
Hom.:
0
Cov.:
30
AF XY:
0.0000151
AC XY:
11
AN XY:
727232
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:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152100
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74294
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:
0.000108
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
Sep 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1784G>A (p.R595Q) alteration is located in exon 10 (coding exon 10) of the NT5C1B gene. This alteration results from a G to A substitution at nucleotide position 1784, causing the arginine (R) at amino acid position 595 to be replaced by a glutamine (Q). 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
0.15
BayesDel_addAF
Benign
0.0033
T
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.097
.;.;T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.93
D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Uncertain
0.46
T;T;T
MetaSVM
Benign
-0.29
T
MutationAssessor
Uncertain
2.0
.;.;M
PROVEAN
Uncertain
-2.5
D;D;D
REVEL
Benign
0.23
Sift
Benign
0.077
T;T;T
Sift4G
Benign
0.10
T;T;T
Polyphen
1.0
.;D;D
Vest4
0.60
MutPred
0.64
Gain of ubiquitination at K576 (P = 0.0522);.;Gain of ubiquitination at K576 (P = 0.0522);
MVP
0.33
MPC
0.47
ClinPred
0.95
D
GERP RS
5.3
Varity_R
0.28
gMVP
0.76

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: rs1471136417; hg19: chr2-18745162; COSMIC: COSV58396147; COSMIC: COSV58396147; API