1-39666223-T-G

Position:

• chr1-39666223-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032526.3(NT5C1A):​c.149A>C​(p.Asn50Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NT5C1A NM_032526.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.18

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23308706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NT5C1A	NM_032526.3	c.149A>C	p.Asn50Thr	missense_variant	2/6	ENST00000235628.2	NP_115915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NT5C1A	ENST00000235628.2	c.149A>C	p.Asn50Thr	missense_variant	2/6	1	NM_032526.3	ENSP00000235628.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2024

The c.149A>C (p.N50T) alteration is located in exon 2 (coding exon 2) of the NT5C1A gene. This alteration results from a A to C substitution at nucleotide position 149, causing the asparagine (N) at amino acid position 50 to be replaced by a threonine (T). 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	0.13
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.9	M
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.074
Sift	Benign	0.065	T
Sift4G	Benign	0.065	T
Polyphen		0.21	B
Vest4		0.53
MutPred		0.28		Gain of sheet (P = 0.0477);
MVP		0.20
MPC		0.48
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.41
gMVP		0.37

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: chr1-40131895;