rs3750118

Variant names:

• chr7-33021623-T-C
• rs3750118
• NM_001002010.5:c.355-266A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001002010.5(NT5C3A):​c.355-266A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 151,956 control chromosomes in the GnomAD database, including 38,888 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.71 (38888 hom., cov: 32)
• Consequence: NT5C3A NM_001002010.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.12
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 7-33021623-T-C is Benign according to our data. Variant chr7-33021623-T-C is described in ClinVar as Benign. ClinVar VariationId is 1296003.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C3A	NM_001002010.5	c.355-266A>G		intron_variant	Intron 4 of 8	ENST00000610140.7	NP_001002010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C3A	ENST00000610140.7	c.355-266A>G		intron_variant	Intron 4 of 8	1	NM_001002010.5	ENSP00000476480.2

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108123 AN: 151838 Hom.: 38849 Cov.: 32

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.686

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.712 AC: 108218 AN: 151956 Hom.: 38888 Cov.: 32 AF XY: 0.713 AC XY: 52919 AN XY: 74264

African (AFR) AF: 0.770 AC: 31916 AN: 41460

American (AMR) AF: 0.728 AC: 11114 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1941 AN: 3470

East Asian (EAS) AF: 0.490 AC: 2531 AN: 5168

South Asian (SAS) AF: 0.606 AC: 2921 AN: 4822

European-Finnish (FIN) AF: 0.759 AC: 8011 AN: 10554

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.703 AC: 47708 AN: 67906

Other (OTH) AF: 0.681 AC: 1436 AN: 2110

Alfa AF: 0.716 Hom.: 5076

Bravo AF: 0.712

Asia WGS AF: 0.546 AC: 1894 AN: 3462

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.5
DANN	Benign	0.79
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs3750118; hg19: chr7-33061235;