rs4236335

Variant names:

• chr7-33027518-C-A
• rs4236335
• NM_001002010.5:c.139-603G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

NT5C3A Gene-Disease associations (from GenCC):

• hemolytic anemia due to pyrimidine 5' nucleotidase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002010.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C3A	NM_001002010.5	MANE Select	c.139-603G>T		intron	N/A	NP_001002010.2	X6RM59
	NT5C3A	NM_001374335.1		c.139-3410G>T		intron	N/A	NP_001361264.1
	NT5C3A	NM_001002009.3		c.37-603G>T		intron	N/A	NP_001002009.1	Q9H0P0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C3A	ENST00000610140.7	TSL:1 MANE Select	c.139-603G>T		intron	N/A	ENSP00000476480.2	X6RM59
	NT5C3A	ENST00000456458.5	TSL:1	n.*44-603G>T		intron	N/A	ENSP00000389676.2	F8WDR0
	NT5C3A	ENST00000930183.1		c.139-603G>T		intron	N/A	ENSP00000600242.1

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

African (AFR) AF: 0.769 AC: 31936 AN: 41508

American (AMR) AF: 0.728 AC: 11128 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1942 AN: 3470

East Asian (EAS) AF: 0.489 AC: 2528 AN: 5170

South Asian (SAS) AF: 0.605 AC: 2912 AN: 4812

European-Finnish (FIN) AF: 0.760 AC: 8014 AN: 10550

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47772 AN: 67990

Other (OTH) AF: 0.679 AC: 1435 AN: 2114

Alfa AF: 0.717 Hom.: 7687

Bravo AF: 0.712

Asia WGS AF: 0.547 AC: 1903 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.4
DANN	Benign	0.66
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4236335;

hg19: chr7-33067130;