7-33015552-T-C

Variant names:

• chr7-33015552-T-C
• rs7790368
• NM_001002010.5:c.894+118A>G

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.894+118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 655,036 control chromosomes in the GnomAD database, including 177,183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.76 (44438 hom., cov: 30)
  • Exomes 𝑓: 0.72 (132745 hom.)
• Consequence: NT5C3A NM_001002010.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.08
• 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=-0.99).
• BP6: Variant 7-33015552-T-C is Benign according to our data. Variant chr7-33015552-T-C is described in ClinVar as Benign. ClinVar VariationId is 1253137.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.846 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.894+118A>G		intron	N/A	NP_001002010.2	X6RM59
	NT5C3A	NM_001374335.1		c.795+118A>G		intron	N/A	NP_001361264.1
	NT5C3A	NM_001002009.3		c.792+118A>G		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.894+118A>G		intron	N/A	ENSP00000476480.2	X6RM59
	NT5C3A	ENST00000456458.5	TSL:1	n.*799+118A>G		intron	N/A	ENSP00000389676.2	F8WDR0
	NT5C3A	ENST00000930183.1		c.861+118A>G		intron	N/A	ENSP00000600242.1

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115599 AN: 151850 Hom.: 44385 Cov.: 30

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.735

GnomAD4 exome AF: 0.724 AC: 364003 AN: 503068 Hom.: 132745 AF XY: 0.724 AC XY: 193486 AN XY: 267210

African (AFR) AF: 0.852 AC: 11264 AN: 13214

American (AMR) AF: 0.795 AC: 17000 AN: 21378

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 8825 AN: 14872

East Asian (EAS) AF: 0.655 AC: 20577 AN: 31408

South Asian (SAS) AF: 0.749 AC: 35271 AN: 47080

European-Finnish (FIN) AF: 0.764 AC: 31782 AN: 41620

Middle Eastern (MID) AF: 0.677 AC: 1393 AN: 2058

European-Non Finnish (NFE) AF: 0.717 AC: 218035 AN: 303920

Other (OTH) AF: 0.722 AC: 19856 AN: 27518

GnomAD4 genome AF: 0.761 AC: 115709 AN: 151968 Hom.: 44438 Cov.: 30 AF XY: 0.764 AC XY: 56697 AN XY: 74256

African (AFR) AF: 0.854 AC: 35392 AN: 41464

American (AMR) AF: 0.773 AC: 11805 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2109 AN: 3468

East Asian (EAS) AF: 0.644 AC: 3315 AN: 5148

South Asian (SAS) AF: 0.743 AC: 3576 AN: 4810

European-Finnish (FIN) AF: 0.767 AC: 8086 AN: 10536

Middle Eastern (MID) AF: 0.712 AC: 208 AN: 292

European-Non Finnish (NFE) AF: 0.724 AC: 49198 AN: 67962

Other (OTH) AF: 0.735 AC: 1552 AN: 2112

Alfa AF: 0.729 Hom.: 50541

Bravo AF: 0.763

Asia WGS AF: 0.689 AC: 2397 AN: 3476

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	-0.99
CADD	Benign	0.22
DANN	Benign	0.38
PhyloP100		-2.1
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: rs7790368; hg19: chr7-33055164;