rs6946062

Variant names:

• chr7-33043495-T-C
• rs6946062
• NM_001002010.5:c.139-16580A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001002010.5(NT5C3A):​c.139-16580A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,992 control chromosomes in the GnomAD database, including 10,225 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10225 hom., cov: 32)
• Consequence: NT5C3A NM_001002010.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.385
• Publications: 7 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

ENSG00000298118 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C3A	NM_001002010.5	c.139-16580A>G		intron_variant	Intron 1 of 8	ENST00000610140.7	NP_001002010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C3A	ENST00000610140.7	c.139-16580A>G		intron_variant	Intron 1 of 8	1	NM_001002010.5	ENSP00000476480.2
NT5C3A	ENST00000456458.5	n.154-7507A>G		intron_variant	Intron 1 of 9	1		ENSP00000389676.2
ENSG00000298118	ENST00000753090.1	n.285+4390T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54414 AN: 151874 Hom.: 10221 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.358 AC: 54459 AN: 151992 Hom.: 10225 Cov.: 32 AF XY: 0.358 AC XY: 26636 AN XY: 74300

African (AFR) AF: 0.295 AC: 12221 AN: 41446

American (AMR) AF: 0.227 AC: 3474 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1074 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2120 AN: 5158

South Asian (SAS) AF: 0.338 AC: 1628 AN: 4818

European-Finnish (FIN) AF: 0.470 AC: 4953 AN: 10544

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 28033 AN: 67962

Other (OTH) AF: 0.323 AC: 682 AN: 2112

Alfa AF: 0.392 Hom.: 28101

Bravo AF: 0.337

Asia WGS AF: 0.322 AC: 1121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.6
DANN	Benign	0.62
PhyloP100		0.39
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: rs6946062; hg19: chr7-33083107;