2-18564038-T-C

Variant summary

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

The NM_033253.4(NT5C1B):​c.1411A>G​(p.Ile471Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,604 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

NT5C1B
NM_033253.4 missense

Scores

1
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02
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.1411A>G p.Ile471Val 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.1411A>G p.Ile471Val missense_variant Exon 9 of 9 1 NM_033253.4 ENSP00000305979.4 Q96P26-2
NT5C1B-RDH14ENST00000532967.5 linkc.1591A>G p.Ile531Val missense_variant Exon 10 of 11 2 ENSP00000433415.1
NT5C1BENST00000406971.6 linkn.*732A>G non_coding_transcript_exon_variant Exon 10 of 10 5 ENSP00000383905.2 C4AM88
NT5C1BENST00000406971.6 linkn.*732A>G 3_prime_UTR_variant Exon 10 of 10 5 ENSP00000383905.2 C4AM88

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250794
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135586
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1460604
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726530
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000225
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 18, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1642A>G (p.I548V) alteration is located in exon 10 (coding exon 10) of the NT5C1B gene. This alteration results from a A to G substitution at nucleotide position 1642, causing the isoleucine (I) at amino acid position 548 to be replaced by a valine (V). 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
0.18
BayesDel_addAF
Benign
-0.036
T
BayesDel_noAF
Benign
-0.12
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
.;.;T
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.84
T;D;D
M_CAP
Benign
0.0087
T
MetaRNN
Uncertain
0.65
D;D;D
MetaSVM
Benign
-0.41
T
MutationAssessor
Uncertain
2.4
.;.;M
PROVEAN
Benign
-0.90
N;N;N
REVEL
Benign
0.28
Sift
Benign
0.072
T;T;T
Sift4G
Uncertain
0.0080
D;D;D
Polyphen
1.0, 1.0
.;D;D
Vest4
0.66
MutPred
0.68
Gain of sheet (P = 0.0477);.;Gain of sheet (P = 0.0477);
MVP
0.30
MPC
0.59
ClinPred
0.86
D
GERP RS
5.0
Varity_R
0.18
gMVP
0.63

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: rs772555868; hg19: chr2-18745304; API