rs10230500

Variant names:

• chr7-33041406-T-C
• rs10230500
• NM_001002010.5:c.139-14491A>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.139-14491A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 152,066 control chromosomes in the GnomAD database, including 40,205 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 0.72 (40205 hom., cov: 31)
• Consequence: NT5C3A NM_001002010.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 9 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C3A	NM_001002010.5	c.139-14491A>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.139-14491A>G		intron_variant	Intron 1 of 8	1	NM_001002010.5	ENSP00000476480.2
NT5C3A	ENST00000456458.5	n.154-5418A>G		intron_variant	Intron 1 of 9	1		ENSP00000389676.2
ENSG00000298118	ENST00000753090.1	n.285+2301T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110095 AN: 151948 Hom.: 40156 Cov.: 31

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.696

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

GnomAD4 genome AF: 0.725 AC: 110202 AN: 152066 Hom.: 40205 Cov.: 31 AF XY: 0.726 AC XY: 53964 AN XY: 74316

African (AFR) AF: 0.787 AC: 32629 AN: 41480

American (AMR) AF: 0.748 AC: 11420 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1967 AN: 3468

East Asian (EAS) AF: 0.625 AC: 3236 AN: 5178

South Asian (SAS) AF: 0.623 AC: 3002 AN: 4818

European-Finnish (FIN) AF: 0.760 AC: 8021 AN: 10550

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.703 AC: 47822 AN: 67984

Other (OTH) AF: 0.693 AC: 1464 AN: 2114

Alfa AF: 0.704 Hom.: 102949

Bravo AF: 0.726

Asia WGS AF: 0.626 AC: 2181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.51
DANN	Benign	0.47
PhyloP100		-1.4
PromoterAI		0.030	Neutral
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: rs10230500; hg19: chr7-33081018;