7-33015182-T-C

Variant names:

• chr7-33015182-T-C
• rs191440599
• NM_001002010.5:c.895-351A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001002010.5(NT5C3A):​c.895-351A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 152,242 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.0049 (25 hom., cov: 32)
• Consequence: NT5C3A NM_001002010.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.25
• Publications: 0 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=-0.92).
• BP6: Variant 7-33015182-T-C is Benign according to our data. Variant chr7-33015182-T-C is described in ClinVar as Benign. ClinVar VariationId is 1239275.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00487 (742/152242) while in subpopulation EAS AF = 0.00521 (27/5186). AF 95% confidence interval is 0.00367. There are 25 homozygotes in GnomAd4. There are 536 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 25 AR gene

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.895-351A>G		intron	N/A	NP_001002010.2	X6RM59
	NT5C3A	NM_001374335.1		c.796-351A>G		intron	N/A	NP_001361264.1
	NT5C3A	NM_001002009.3		c.793-351A>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.895-351A>G		intron	N/A	ENSP00000476480.2	X6RM59
	NT5C3A	ENST00000456458.5	TSL:1	n.*800-351A>G		intron	N/A	ENSP00000389676.2	F8WDR0
	NT5C3A	ENST00000930183.1		c.862-351A>G		intron	N/A	ENSP00000600242.1

Frequencies

GnomAD3 genomes AF: 0.00488 AC: 742 AN: 152124 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00519

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0575

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00140

Gnomad OTH AF: 0.00335

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

GnomAD4 genome AF: 0.00487 AC: 742 AN: 152242 Hom.: 25 Cov.: 32 AF XY: 0.00720 AC XY: 536 AN XY: 74432

African (AFR) AF: 0.0000241 AC: 1 AN: 41544

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00521 AC: 27 AN: 5186

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.0575 AC: 609 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00140 AC: 95 AN: 68028

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00476 Hom.: 2

Bravo AF: 0.000450

Asia WGS AF: 0.00664 AC: 23 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	-0.92
CADD	Benign	0.039
DANN	Benign	0.75
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism

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: rs191440599; hg19: chr7-33054794;