7-33014750-T-G

Variant names:

• chr7-33014750-T-G
• rs563703074
• NM_001002010.5:c.976A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001002010.5(NT5C3A):​c.976A>C​(p.Ile326Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. I326V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NT5C3A NM_001002010.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07

Genes affected

NT5C3A (HGNC:17820): (5'-nucleotidase, cytosolic IIIA) This gene encodes a member of the 5'-nucleotidase family of enzymes that catalyze the dephosphorylation of nucleoside 5'-monophosphates. The encoded protein is the type 1 isozyme of pyrimidine 5' nucleotidase and catalyzes the dephosphorylation of pyrimidine 5' monophosphates. Mutations in this gene are a cause of hemolytic anemia due to uridine 5-prime monophosphate hydrolase deficiency. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and pseudogenes of this gene are located on the long arm of chromosomes 3 and 4. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2833431).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C3A	NM_001002010.5	c.976A>C	p.Ile326Leu	missense_variant	Exon 9 of 9	ENST00000610140.7	NP_001002010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C3A	ENST00000610140.7	c.976A>C	p.Ile326Leu	missense_variant	Exon 9 of 9	1	NM_001002010.5	ENSP00000476480.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.30	T;.;.;T;.;T;.;.
Eigen	Benign	-0.0059
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.58	.;T;T;T;.;T;.;.
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.28	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.3	.;.;.;L;.;.;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.0	.;N;N;.;.;.;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.34	.;T;T;.;.;.;T;T
Sift4G	Benign	0.65	.;T;T;T;.;T;T;T
Polyphen		0.085, 0.10	.;.;B;B;B;.;B;.
Vest4		0.35, 0.41, 0.36, 0.41, 0.48
MutPred		0.59		.;.;.;Loss of catalytic residue at L336 (P = 0.0648);.;.;.;.;
MVP		0.76
MPC		0.25
ClinPred		0.53	D
GERP RS		5.9
Varity_R		0.44
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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

Other links and lift over

dbSNP: rs563703074; hg19: chr7-33054362;