7-33014500-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001002010.5(NT5C3A):c.*230T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 149,234 control chromosomes in the GnomAD database, including 39,891 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.73 (39891 hom., cov: 32)
  • Exomes 𝑓: 0.69 (102147 hom.)
  • Failed GnomAD Quality Control
• Consequence: NT5C3A NM_001002010.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.505

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-33014500-A-G is Benign according to our data. Variant chr7-33014500-A-G is described in ClinVar as [Benign]. Clinvar id is 1178214.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NT5C3A	NM_001002010.5	c.*230T>C		3_prime_UTR_variant	9/9	ENST00000610140.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NT5C3A	ENST00000610140.7	c.*230T>C		3_prime_UTR_variant	9/9	1	NM_001002010.5	P3
NT5C3A	ENST00000456458.5	c.*1131T>C		3_prime_UTR_variant, NMD_transcript_variant	10/10	1
NT5C3A	ENST00000409467.6	c.*230T>C		3_prime_UTR_variant	11/11	5		A1
NT5C3A	ENST00000643244.1	c.*230T>C		3_prime_UTR_variant	10/10

Frequencies

GnomAD3 genomes AF: 0.734 AC: 109437 AN: 149112 Hom.: 39841 Cov.: 32

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.704

GnomAD3 exomes AF: 0.703 AC: 80312 AN: 114184 Hom.: 28932 AF XY: 0.695 AC XY: 42889 AN XY: 61700

Gnomad AFR exome AF: 0.793

Gnomad AMR exome AF: 0.803

Gnomad ASJ exome AF: 0.577

Gnomad EAS exome AF: 0.623

Gnomad SAS exome AF: 0.635

Gnomad FIN exome AF: 0.763

Gnomad NFE exome AF: 0.702

Gnomad OTH exome AF: 0.689

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.692 AC: 291774 AN: 421842 Hom.: 102147 Cov.: 4 AF XY: 0.685 AC XY: 158222 AN XY: 231126

Gnomad4 AFR exome AF: 0.786

Gnomad4 AMR exome AF: 0.799

Gnomad4 ASJ exome AF: 0.570

Gnomad4 EAS exome AF: 0.645

Gnomad4 SAS exome AF: 0.629

Gnomad4 FIN exome AF: 0.757

Gnomad4 NFE exome AF: 0.696

Gnomad4 OTH exome AF: 0.687

GnomAD4 genome AF: 0.734 AC: 109546 AN: 149234 Hom.: 39891 Cov.: 32 AF XY: 0.736 AC XY: 53615 AN XY: 72822

Gnomad4 AFR AF: 0.807

Gnomad4 AMR AF: 0.753

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.643

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.702

Alfa AF: 0.688 Hom.: 6620

Bravo AF: 0.726

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	11
Dann	Benign	0.81

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: rs12536321; hg19: chr7-33054112;