7-33014500-A-G

Variant names:

• chr7-33014500-A-G
• rs12536321
• NM_001002010.5:c.*230T>C

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.*230T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 149,234 control chromosomes in the GnomAD database, including 39,891 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.73 (39891 hom., cov: 32)
  • Exomes 𝑓: 0.69 (102147 hom.)
  • Failed GnomAD Quality Control
• Consequence: NT5C3A NM_001002010.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.505
• Publications: 6 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-33014500-A-G is Benign according to our data. Variant chr7-33014500-A-G is described in ClinVar as Benign. ClinVar VariationId is 1178214.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002010.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C3A	NM_001002010.5	MANE Select	c.*230T>C		3_prime_UTR	Exon 9 of 9	NP_001002010.2	X6RM59
	NT5C3A	NM_001374335.1		c.*230T>C		3_prime_UTR	Exon 8 of 8	NP_001361264.1
	NT5C3A	NM_001002009.3		c.*230T>C		3_prime_UTR	Exon 10 of 10	NP_001002009.1	Q9H0P0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C3A	ENST00000610140.7	TSL:1 MANE Select	c.*230T>C		3_prime_UTR	Exon 9 of 9	ENSP00000476480.2	X6RM59
	NT5C3A	ENST00000456458.5	TSL:1	n.*1131T>C		non_coding_transcript_exon	Exon 10 of 10	ENSP00000389676.2	F8WDR0
	NT5C3A	ENST00000456458.5	TSL:1	n.*1131T>C		3_prime_UTR	Exon 10 of 10	ENSP00000389676.2	F8WDR0

Frequencies

GnomAD3 genomes AF: 0.734 AC: 109437 AN: 149112 Hom.: 39841 Cov.: 32

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.704

GnomAD2 exomes AF: 0.703 AC: 80312 AN: 114184 AF XY: 0.695

Gnomad AFR exome AF: 0.793

Gnomad AMR exome AF: 0.803

Gnomad ASJ exome AF: 0.577

Gnomad EAS exome AF: 0.623

Gnomad FIN exome AF: 0.763

Gnomad NFE exome AF: 0.702

Gnomad OTH exome AF: 0.689

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.692 AC: 291774 AN: 421842 Hom.: 102147 Cov.: 4 AF XY: 0.685 AC XY: 158222 AN XY: 231126

African (AFR) AF: 0.786 AC: 10042 AN: 12774

American (AMR) AF: 0.799 AC: 24183 AN: 30274

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 8812 AN: 15470

East Asian (EAS) AF: 0.645 AC: 12216 AN: 18942

South Asian (SAS) AF: 0.629 AC: 37657 AN: 59842

European-Finnish (FIN) AF: 0.757 AC: 13415 AN: 17732

Middle Eastern (MID) AF: 0.617 AC: 1089 AN: 1766

European-Non Finnish (NFE) AF: 0.696 AC: 169136 AN: 242892

Other (OTH) AF: 0.687 AC: 15224 AN: 22150

GnomAD4 genome AF: 0.734 AC: 109546 AN: 149234 Hom.: 39891 Cov.: 32 AF XY: 0.736 AC XY: 53615 AN XY: 72822

African (AFR) AF: 0.807 AC: 32430 AN: 40202

American (AMR) AF: 0.753 AC: 11334 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1964 AN: 3442

East Asian (EAS) AF: 0.643 AC: 3196 AN: 4970

South Asian (SAS) AF: 0.651 AC: 2985 AN: 4584

European-Finnish (FIN) AF: 0.766 AC: 7972 AN: 10410

Middle Eastern (MID) AF: 0.657 AC: 180 AN: 274

European-Non Finnish (NFE) AF: 0.707 AC: 47572 AN: 67332

Other (OTH) AF: 0.702 AC: 1458 AN: 2078

Alfa AF: 0.688 Hom.: 6620

Bravo AF: 0.726

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		0.51
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: rs12536321; hg19: chr7-33054112;