1-39666184-C-A

Variant names:

• chr1-39666184-C-A
• rs955631482
• NM_032526.3:c.188G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032526.3(NT5C1A):​c.188G>T​(p.Arg63Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000381 in 1,573,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R63H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000016 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: NT5C1A NM_032526.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 3 publications found

Genes affected

NT5C1A (HGNC:17819): (5'-nucleotidase, cytosolic IA) Cytosolic nucleotidases, such as NT5C1A, dephosphorylate nucleoside monophosphates (Hunsucker et al., 2001 [PubMed 11133996]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3039356).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032526.3. 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
	NT5C1A	NM_032526.3	MANE Select	c.188G>T	p.Arg63Leu	missense	Exon 2 of 6	NP_115915.1	Q9BXI3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C1A	ENST00000235628.2	TSL:1 MANE Select	c.188G>T	p.Arg63Leu	missense	Exon 2 of 6	ENSP00000235628.1	Q9BXI3
	NT5C1A	ENST00000905835.1		c.188G>T	p.Arg63Leu	missense	Exon 3 of 7	ENSP00000575894.1

Frequencies

GnomAD3 genomes AF: 0.0000161 AC: 2 AN: 124334 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000159

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

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250646 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000276 AC: 4 AN: 1449564 Hom.: 0 Cov.: 32 AF XY: 0.00000416 AC XY: 3 AN XY: 721080

African (AFR) AF: 0.00 AC: 0 AN: 33072

American (AMR) AF: 0.0000916 AC: 4 AN: 43690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25872

East Asian (EAS) AF: 0.00 AC: 0 AN: 39028

South Asian (SAS) AF: 0.00 AC: 0 AN: 84528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105256

Other (OTH) AF: 0.00 AC: 0 AN: 59762

GnomAD4 genome AF: 0.0000161 AC: 2 AN: 124334 Hom.: 0 Cov.: 31 AF XY: 0.0000329 AC XY: 2 AN XY: 60766

African (AFR) AF: 0.00 AC: 0 AN: 32526

American (AMR) AF: 0.000159 AC: 2 AN: 12550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2892

East Asian (EAS) AF: 0.00 AC: 0 AN: 4070

South Asian (SAS) AF: 0.00 AC: 0 AN: 4006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 56652

Other (OTH) AF: 0.00 AC: 0 AN: 1654

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000102

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.074
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.030	D
Polyphen		0.0020	B
Vest4		0.60
MutPred		0.47		Loss of MoRF binding (P = 0.0332)
MVP		0.11
MPC		0.48
ClinPred		0.65	D
GERP RS		2.7
Varity_R		0.21
gMVP		0.51
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs955631482; hg19: chr1-40131856;