chr2-18563821-C-A

Variant names:

• chr2-18563821-C-A
• rs79501117
• NM_033253.4:c.1628G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_033253.4(NT5C1B):​c.1628G>T​(p.Gly543Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,578,180 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: NT5C1B NM_033253.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.41
• Publications: 2 publications found

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]

ENSG00000304698 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033253.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C1B	NM_033253.4	MANE Select	c.1628G>T	p.Gly543Val	missense	Exon 9 of 9	NP_150278.2	Q96P26-2
	NT5C1B	NM_001199087.2		c.1859G>T	p.Gly620Val	missense	Exon 10 of 10	NP_001186016.1	B4DZ86
	NT5C1B	NM_001199088.2		c.1814G>T	p.Gly605Val	missense	Exon 10 of 10	NP_001186017.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C1B	ENST00000304081.9	TSL:1 MANE Select	c.1628G>T	p.Gly543Val	missense	Exon 9 of 9	ENSP00000305979.4	Q96P26-2
	NT5C1B	ENST00000359846.6	TSL:1	c.1808G>T	p.Gly603Val	missense	Exon 10 of 10	ENSP00000352904.2	Q96P26-1
	NT5C1B-RDH14	ENST00000532967.5	TSL:2	c.1784+24G>T		intron	N/A	ENSP00000433415.1

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000988 AC: 23 AN: 232704 AF XY: 0.000143

Gnomad AFR exome AF: 0.0000627

Gnomad AMR exome AF: 0.0000325

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000341

Gnomad NFE exome AF: 0.000131

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000130 AC: 186 AN: 1425890 Hom.: 0 Cov.: 30 AF XY: 0.000129 AC XY: 91 AN XY: 705608

African (AFR) AF: 0.00 AC: 0 AN: 32060

American (AMR) AF: 0.0000500 AC: 2 AN: 40026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39174

South Asian (SAS) AF: 0.00 AC: 0 AN: 82012

European-Finnish (FIN) AF: 0.000382 AC: 20 AN: 52312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5564

European-Non Finnish (NFE) AF: 0.000143 AC: 156 AN: 1092044

Other (OTH) AF: 0.000137 AC: 8 AN: 58602

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152290 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74472

African (AFR) AF: 0.0000722 AC: 3 AN: 41556

American (AMR) AF: 0.000458 AC: 7 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68026

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000184 Hom.: 0

Bravo AF: 0.000136

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000124 AC: 15

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Pathogenic	0.25
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Uncertain	0.47	D
MutationAssessor	Pathogenic	3.4	M
PhyloP100		2.4
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.029	D
Polyphen		1.0	D
Vest4		0.51
MVP		0.40
MPC		0.83
ClinPred		0.91	D
GERP RS		4.9
Varity_R		0.70
gMVP		0.95
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

dbSNP: rs79501117; hg19: chr2-18745087;