2-18576819-C-G

Variant summary

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

The NM_033253.4(NT5C1B):​c.1098G>C​(p.Leu366Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000725 in 1,613,778 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

NT5C1B
NM_033253.4 missense

Scores

4
6
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.10
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.1098G>C p.Leu366Phe missense_variant Exon 7 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.1098G>C p.Leu366Phe missense_variant Exon 7 of 9 1 NM_033253.4 ENSP00000305979.4 Q96P26-2
NT5C1B-RDH14ENST00000532967.5 linkc.1278G>C p.Leu426Phe missense_variant Exon 8 of 11 2 ENSP00000433415.1
NT5C1BENST00000406971.6 linkn.*419G>C non_coding_transcript_exon_variant Exon 8 of 10 5 ENSP00000383905.2 C4AM88
NT5C1BENST00000406971.6 linkn.*419G>C 3_prime_UTR_variant Exon 8 of 10 5 ENSP00000383905.2 C4AM88

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152170
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251238
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135774
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000174
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000718
AC:
105
AN:
1461608
Hom.:
0
Cov.:
31
AF XY:
0.0000633
AC XY:
46
AN XY:
727090
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000157
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:
0.0000791
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.0000789
AC:
12
AN:
152170
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000130
Hom.:
0
Bravo
AF:
0.0000642
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 26, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1329G>C (p.L443F) alteration is located in exon 8 (coding exon 8) of the NT5C1B gene. This alteration results from a G to C substitution at nucleotide position 1329, causing the leucine (L) at amino acid position 443 to be replaced by a phenylalanine (F). 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
0.21
BayesDel_addAF
Benign
-0.076
T
BayesDel_noAF
Benign
-0.090
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.52
.;.;.;D
Eigen
Benign
-0.095
Eigen_PC
Benign
-0.25
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.85
D;D;D;D
M_CAP
Uncertain
0.13
D
MetaRNN
Uncertain
0.67
D;D;D;D
MetaSVM
Uncertain
-0.18
T
MutationAssessor
Pathogenic
3.6
.;.;.;H
PROVEAN
Uncertain
-3.9
D;D;D;D
REVEL
Pathogenic
0.65
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
0.23, 0.96, 0.99
.;B;D;D
Vest4
0.38
MutPred
0.92
Loss of stability (P = 0.2118);.;.;Loss of stability (P = 0.2118);
MVP
0.72
MPC
0.65
ClinPred
0.98
D
GERP RS
-1.8
Varity_R
0.74
gMVP
0.91

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: rs140510680; hg19: chr2-18758085; API