7-33015703-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001002010.5(NT5C3A):c.861G>A(p.Glu287=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00595 in 1,610,512 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (77 hom.)
• Consequence: NT5C3A NM_001002010.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0450

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 7-33015703-C-T is Benign according to our data. Variant chr7-33015703-C-T is described in ClinVar as [Benign]. Clinvar id is 780675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.045 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00403 (614/152296) while in subpopulation SAS AF= 0.0302 (146/4832). AF 95% confidence interval is 0.0262. There are 4 homozygotes in gnomad4. There are 328 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NT5C3A	NM_001002010.5	c.861G>A	p.Glu287=	synonymous_variant	8/9	ENST00000610140.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NT5C3A	ENST00000610140.7	c.861G>A	p.Glu287=	synonymous_variant	8/9	1	NM_001002010.5	P3

Frequencies

GnomAD3 genomes AF: 0.00402 AC: 611 AN: 152178 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000821

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0300

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00495

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00671 AC: 1685 AN: 251248 Hom.: 27 AF XY: 0.00760 AC XY: 1032 AN XY: 135802

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00608

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.000435

Gnomad SAS exome AF: 0.0289

Gnomad FIN exome AF: 0.000647

Gnomad NFE exome AF: 0.00452

Gnomad OTH exome AF: 0.00669

GnomAD4 exome AF: 0.00615 AC: 8965 AN: 1458216 Hom.: 77 Cov.: 28 AF XY: 0.00685 AC XY: 4973 AN XY: 725714

Gnomad4 AFR exome AF: 0.000838

Gnomad4 AMR exome AF: 0.00606

Gnomad4 ASJ exome AF: 0.000651

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0286

Gnomad4 FIN exome AF: 0.000711

Gnomad4 NFE exome AF: 0.00519

Gnomad4 OTH exome AF: 0.00616

GnomAD4 genome AF: 0.00403 AC: 614 AN: 152296 Hom.: 4 Cov.: 32 AF XY: 0.00440 AC XY: 328 AN XY: 74482

Gnomad4 AFR AF: 0.000818

Gnomad4 AMR AF: 0.00490

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0302

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00495

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00414 Hom.: 0

Bravo AF: 0.00329

Asia WGS AF: 0.0190 AC: 66 AN: 3478

EpiCase AF: 0.00453

EpiControl AF: 0.00415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hemolytic anemia due to pyrimidine 5' nucleotidase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

May 25, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 08, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	2.9
Dann	Benign	0.61

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: rs72555746; hg19: chr7-33055315; COSMIC: COSV99641544; COSMIC: COSV99641544;