7-33062850-C-T

Variant names:

• chr7-33062850-C-T
• rs13228639
• NM_001002010.5:c.-145G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001002010.5(NT5C3A):​c.-145G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 1,413,142 control chromosomes in the GnomAD database, including 342,867 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 0.69 (36292 hom., cov: 32)
  • Exomes 𝑓: 0.69 (306575 hom.)
• Consequence: NT5C3A NM_001002010.5 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.423
• Publications: 8 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics

ENSG00000302625 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C3A	NM_001002010.5	c.-145G>A		upstream_gene_variant		ENST00000610140.7	NP_001002010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C3A	ENST00000610140.7	c.-145G>A		upstream_gene_variant		1	NM_001002010.5	ENSP00000476480.2

Frequencies

GnomAD3 genomes AF: 0.692 AC: 104490 AN: 151106 Hom.: 36252 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.665

GnomAD4 exome AF: 0.694 AC: 876078 AN: 1261920 Hom.: 306575 AF XY: 0.691 AC XY: 433736 AN XY: 628092

African (AFR) AF: 0.703 AC: 20022 AN: 28492

American (AMR) AF: 0.759 AC: 26685 AN: 35160

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 13381 AN: 23934

East Asian (EAS) AF: 0.498 AC: 17399 AN: 34910

South Asian (SAS) AF: 0.610 AC: 46058 AN: 75486

European-Finnish (FIN) AF: 0.757 AC: 27138 AN: 35866

Middle Eastern (MID) AF: 0.612 AC: 2394 AN: 3910

European-Non Finnish (NFE) AF: 0.708 AC: 687160 AN: 970634

Other (OTH) AF: 0.670 AC: 35841 AN: 53528

GnomAD4 genome AF: 0.692 AC: 104584 AN: 151222 Hom.: 36292 Cov.: 32 AF XY: 0.693 AC XY: 51198 AN XY: 73930

African (AFR) AF: 0.699 AC: 28555 AN: 40864

American (AMR) AF: 0.720 AC: 10994 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1941 AN: 3460

East Asian (EAS) AF: 0.491 AC: 2514 AN: 5116

South Asian (SAS) AF: 0.605 AC: 2908 AN: 4810

European-Finnish (FIN) AF: 0.759 AC: 8019 AN: 10564

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.702 AC: 47630 AN: 67840

Other (OTH) AF: 0.660 AC: 1389 AN: 2106

Alfa AF: 0.617 Hom.: 1829

Bravo AF: 0.686

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.6
DANN	Benign	0.93
PhyloP100		-0.42
PromoterAI		0.17	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13228639; hg19: chr7-33102462; COSMIC: COSV54238608;