rs17170223

Variant names:

• chr7-33035961-A-G
• rs17170223
• ENST00000456458.5:n.*16T>C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000456458.5(NT5C3A):​n.*16T>C variant causes a non coding transcript exon 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 ENST00000456458.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.627
• Publications: 5 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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000456458.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C3A	NM_001002010.5	MANE Select	c.139-9046T>C		intron	N/A	NP_001002010.2
	NT5C3A	NM_001002009.3		c.9T>C	p.Asn3Asn	synonymous	Exon 2 of 10	NP_001002009.1
	NT5C3A	NM_016489.14		c.9T>C	p.Asn3Asn	synonymous	Exon 2 of 10	NP_057573.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C3A	ENST00000456458.5	TSL:1	n.*16T>C		non_coding_transcript_exon	Exon 2 of 10	ENSP00000389676.2
	NT5C3A	ENST00000456458.5	TSL:1	n.*16T>C		3_prime_UTR	Exon 2 of 10	ENSP00000389676.2
	NT5C3A	ENST00000610140.7	TSL:1 MANE Select	c.139-9046T>C		intron	N/A	ENSP00000476480.2

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

GnomAD2 exomes AF: 0.0341 AC: 8573 AN: 251374 AF XY: 0.0388

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 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

African (AFR) AF: 0.0548 AC: 1834 AN: 33448

American (AMR) AF: 0.0135 AC: 605 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0416 AC: 1088 AN: 26126

East Asian (EAS) AF: 0.00989 AC: 392 AN: 39638

South Asian (SAS) AF: 0.123 AC: 10571 AN: 86212

European-Finnish (FIN) AF: 0.00888 AC: 474 AN: 53384

Middle Eastern (MID) AF: 0.0597 AC: 344 AN: 5762

European-Non Finnish (NFE) AF: 0.0213 AC: 23691 AN: 1111464

Other (OTH) AF: 0.0357 AC: 2152 AN: 60342

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

African (AFR) AF: 0.0536 AC: 2223 AN: 41484

American (AMR) AF: 0.0239 AC: 365 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0414 AC: 143 AN: 3456

East Asian (EAS) AF: 0.0187 AC: 97 AN: 5186

South Asian (SAS) AF: 0.120 AC: 578 AN: 4808

European-Finnish (FIN) AF: 0.00756 AC: 80 AN: 10584

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0203 AC: 1378 AN: 67908

Other (OTH) AF: 0.0380 AC: 80 AN: 2106

Alfa AF: 0.0254 Hom.: 157

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

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Nov 15, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	16
DANN	Benign	0.83
PhyloP100		0.63
PromoterAI		-0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=300/0	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

Other links and lift over

dbSNP: rs17170223; hg19: chr7-33075573;