7-33015098-C-T

Variant names:

• chr7-33015098-C-T
• rs2893457
• NM_001002010.5:c.895-267G>A

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.895-267G>A 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 151,932 control chromosomes in the GnomAD database, including 40,172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.72 (40172 hom., cov: 30)
• Consequence: NT5C3A NM_001002010.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.77
• 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: 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=-0.9).
• BP6: Variant 7-33015098-C-T is Benign according to our data. Variant chr7-33015098-C-T is described in ClinVar as Benign. ClinVar VariationId is 1226780.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 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.895-267G>A		intron	N/A	NP_001002010.2	X6RM59
	NT5C3A	NM_001374335.1		c.796-267G>A		intron	N/A	NP_001361264.1
	NT5C3A	NM_001002009.3		c.793-267G>A		intron	N/A	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.895-267G>A		intron	N/A	ENSP00000476480.2	X6RM59
	NT5C3A	ENST00000456458.5	TSL:1	n.*800-267G>A		intron	N/A	ENSP00000389676.2	F8WDR0
	NT5C3A	ENST00000930183.1		c.862-267G>A		intron	N/A	ENSP00000600242.1

Frequencies

GnomAD3 genomes AF: 0.725 AC: 109991 AN: 151814 Hom.: 40123 Cov.: 30

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.704

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: 110098 AN: 151932 Hom.: 40172 Cov.: 30 AF XY: 0.726 AC XY: 53893 AN XY: 74228

African (AFR) AF: 0.786 AC: 32583 AN: 41430

American (AMR) AF: 0.748 AC: 11406 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1968 AN: 3470

East Asian (EAS) AF: 0.624 AC: 3219 AN: 5156

South Asian (SAS) AF: 0.623 AC: 2998 AN: 4816

European-Finnish (FIN) AF: 0.760 AC: 8003 AN: 10530

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47820 AN: 67972

Other (OTH) AF: 0.693 AC: 1458 AN: 2104

Alfa AF: 0.718 Hom.: 5684

Bravo AF: 0.726

Asia WGS AF: 0.626 AC: 2180 AN: 3478

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	-0.90
CADD	Benign	0.090
DANN	Benign	0.51
PhyloP100		-1.8
Mutation Taster		=99/1	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: rs2893457; hg19: chr7-33054710;