1-39659324-C-T

Variant names:

• chr1-39659324-C-T
• NM_032526.3:c.904G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032526.3(NT5C1A):​c.904G>A​(p.Glu302Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NT5C1A NM_032526.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.88

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.819

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C1A	NM_032526.3	c.904G>A	p.Glu302Lys	missense_variant	Exon 6 of 6	ENST00000235628.2	NP_115915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C1A	ENST00000235628.2	c.904G>A	p.Glu302Lys	missense_variant	Exon 6 of 6	1	NM_032526.3	ENSP00000235628.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.904G>A (p.E302K) alteration is located in exon 6 (coding exon 6) of the NT5C1A gene. This alteration results from a G to A substitution at nucleotide position 904, causing the glutamic acid (E) at amino acid position 302 to be replaced by a lysine (K). 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	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0099	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.9	M
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.58
Sift	Benign	0.091	T
Sift4G	Benign	0.16	T
Polyphen		0.83	P
Vest4		0.93
MutPred		0.55		Gain of MoRF binding (P = 0.005);
MVP		0.30
MPC		0.91
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.50
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-40124996;