rs4236335

Positions:

• chr7-33027518-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001002010.5(NT5C3A):​c.139-603G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 152,094 control chromosomes in the GnomAD database, including 38,922 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.71 (38922 hom., cov: 33)
• Consequence: NT5C3A NM_001002010.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.487

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NT5C3A	NM_001002010.5	c.139-603G>T		intron_variant		ENST00000610140.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NT5C3A	ENST00000610140.7	c.139-603G>T		intron_variant		1	NM_001002010.5	P3

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108213 AN: 151976 Hom.: 38883 Cov.: 33

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.684

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.712 AC: 108308 AN: 152094 Hom.: 38922 Cov.: 33 AF XY: 0.713 AC XY: 52974 AN XY: 74346

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.760

Gnomad4 NFE AF: 0.703

Gnomad4 OTH AF: 0.679

Alfa AF: 0.715 Hom.: 7460

Bravo AF: 0.712

Asia WGS AF: 0.547 AC: 1903 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.4
DANN	Benign	0.66

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

LitVar

Other links and lift over

dbSNP: rs4236335; hg19: chr7-33067130;