rs17170223

chr7-33035961-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001002010.5(NT5C3A):c.139-9046T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 1,613,086 control chromosomes in the GnomAD database, including 1,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (129 hom., cov: 32)
  • Exomes 𝑓: 0.028 (1173 hom.)
• Consequence: NT5C3A NM_001002010.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.627

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BP6: Variant 7-33035961-A-G is Benign according to our data. Variant chr7-33035961-A-G is described in ClinVar as [Benign]. Clinvar id is 995643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.139-9046T>C		intron_variant		ENST00000610140.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NT5C3A	ENST00000610140.7	c.139-9046T>C		intron_variant		1	NM_001002010.5	P3

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 4975 AN: 151870 Hom.: 131 Cov.: 32

Gnomad AFR AF: 0.0537

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0240

Gnomad ASJ AF: 0.0414

Gnomad EAS AF: 0.0187

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.00756

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0355

GnomAD3 exomes AF: 0.0341 AC: 8573 AN: 251374 Hom.: 354 AF XY: 0.0388 AC XY: 5267 AN XY: 135850

Gnomad AFR exome AF: 0.0554

Gnomad AMR exome AF: 0.0129

Gnomad ASJ exome AF: 0.0424

Gnomad EAS exome AF: 0.0196

Gnomad SAS exome AF: 0.124

Gnomad FIN exome AF: 0.00934

Gnomad NFE exome AF: 0.0198

Gnomad OTH exome AF: 0.0315

GnomAD4 exome AF: 0.0282 AC: 41151 AN: 1461098 Hom.: 1173 Cov.: 30 AF XY: 0.0310 AC XY: 22569 AN XY: 726882

Gnomad4 AFR exome AF: 0.0548

Gnomad4 AMR exome AF: 0.0135

Gnomad4 ASJ exome AF: 0.0416

Gnomad4 EAS exome AF: 0.00989

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.00888

Gnomad4 NFE exome AF: 0.0213

Gnomad4 OTH exome AF: 0.0357

GnomAD4 genome AF: 0.0327 AC: 4977 AN: 151988 Hom.: 129 Cov.: 32 AF XY: 0.0329 AC XY: 2446 AN XY: 74300

Gnomad4 AFR AF: 0.0536

Gnomad4 AMR AF: 0.0239

Gnomad4 ASJ AF: 0.0414

Gnomad4 EAS AF: 0.0187

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.00756

Gnomad4 NFE AF: 0.0203

Gnomad4 OTH AF: 0.0380

Alfa AF: 0.0256 Hom.: 43

Bravo AF: 0.0322

Asia WGS AF: 0.0640 AC: 222 AN: 3478

EpiCase AF: 0.0240

EpiControl AF: 0.0225

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

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

Nov 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
Cadd	Benign	16
Dann	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs17170223; hg19: chr7-33075573;