rs6946062

Positions:

• chr7-33043495-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000610140.7(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 ENST00000610140.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.385

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 -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/exons	MANE	Protein	UniProt
NT5C3A	NM_001002010.5	c.139-16580A>G		intron_variant		ENST00000610140.7	NP_001002010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NT5C3A	ENST00000610140.7	c.139-16580A>G		intron_variant		1	NM_001002010.5	ENSP00000476480	P3
NT5C3A	ENST00000456458.5	c.154-7507A>G		intron_variant, NMD_transcript_variant		1		ENSP00000389676

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

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.323

Alfa AF: 0.387 Hom.: 10874

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

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: rs6946062; hg19: chr7-33083107;