rs11974256

Positions:

• chr7-33022213-C-T

Variant summary

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

The NM_001002010.5(NT5C3A):​c.308-114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0309 in 671,232 control chromosomes in the GnomAD database, including 728 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 0.028 (91 hom., cov: 33)
  • Exomes 𝑓: 0.032 (637 hom.)
• Consequence: NT5C3A NM_001002010.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NT5C3A	NM_001002010.5	c.308-114G>A		intron_variant		ENST00000610140.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NT5C3A	ENST00000610140.7	c.308-114G>A		intron_variant		1	NM_001002010.5	P3

Frequencies

GnomAD3 genomes AF: 0.0284 AC: 4328 AN: 152160 Hom.: 93 Cov.: 33

Gnomad AFR AF: 0.0385

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.0185

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.00744

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0202

Gnomad OTH AF: 0.0335

GnomAD4 exome AF: 0.0316 AC: 16414 AN: 518954 Hom.: 637 AF XY: 0.0372 AC XY: 10442 AN XY: 281026

Gnomad4 AFR exome AF: 0.0382

Gnomad4 AMR exome AF: 0.0142

Gnomad4 ASJ exome AF: 0.0410

Gnomad4 EAS exome AF: 0.00817

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.00845

Gnomad4 NFE exome AF: 0.0198

Gnomad4 OTH exome AF: 0.0343

GnomAD4 genome AF: 0.0284 AC: 4330 AN: 152278 Hom.: 91 Cov.: 33 AF XY: 0.0289 AC XY: 2149 AN XY: 74470

Gnomad4 AFR AF: 0.0384

Gnomad4 AMR AF: 0.0230

Gnomad4 ASJ AF: 0.0412

Gnomad4 EAS AF: 0.0185

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.00744

Gnomad4 NFE AF: 0.0202

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0228 Hom.: 5

Bravo AF: 0.0274

Asia WGS AF: 0.0630 AC: 218 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11974256; hg19: chr7-33061825;