7-33019795-A-G

Variant names:

• chr7-33019795-A-G
• rs2392209
• NM_001002010.5:c.441-71T>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.441-71T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 865,288 control chromosomes in the GnomAD database, including 237,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (46028 hom., cov: 32)
  • Exomes 𝑓: 0.73 (191703 hom.)
• Consequence: NT5C3A NM_001002010.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.737
• Publications: 5 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=-0.86).
• BP6: Variant 7-33019795-A-G is Benign according to our data. Variant chr7-33019795-A-G is described in ClinVar as Benign. ClinVar VariationId is 1269506.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 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.441-71T>C		intron	N/A	NP_001002010.2	X6RM59
	NT5C3A	NM_001374335.1		c.342-71T>C		intron	N/A	NP_001361264.1
	NT5C3A	NM_001002009.3		c.339-71T>C		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.441-71T>C		intron	N/A	ENSP00000476480.2	X6RM59
	NT5C3A	ENST00000456458.5	TSL:1	n.*346-71T>C		intron	N/A	ENSP00000389676.2	F8WDR0
	NT5C3A	ENST00000930183.1		c.441-71T>C		intron	N/A	ENSP00000600242.1

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117524 AN: 152038 Hom.: 45968 Cov.: 32

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.744

GnomAD4 exome AF: 0.731 AC: 521456 AN: 713132 Hom.: 191703 AF XY: 0.730 AC XY: 279214 AN XY: 382268

African (AFR) AF: 0.897 AC: 16953 AN: 18890

American (AMR) AF: 0.815 AC: 34046 AN: 41764

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 12847 AN: 21282

East Asian (EAS) AF: 0.655 AC: 23384 AN: 35716

South Asian (SAS) AF: 0.752 AC: 51644 AN: 68630

European-Finnish (FIN) AF: 0.766 AC: 30510 AN: 39854

Middle Eastern (MID) AF: 0.699 AC: 2951 AN: 4222

European-Non Finnish (NFE) AF: 0.723 AC: 323026 AN: 446818

Other (OTH) AF: 0.726 AC: 26095 AN: 35956

GnomAD4 genome AF: 0.773 AC: 117641 AN: 152156 Hom.: 46028 Cov.: 32 AF XY: 0.775 AC XY: 57654 AN XY: 74368

African (AFR) AF: 0.895 AC: 37149 AN: 41516

American (AMR) AF: 0.777 AC: 11874 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2111 AN: 3470

East Asian (EAS) AF: 0.645 AC: 3342 AN: 5178

South Asian (SAS) AF: 0.744 AC: 3586 AN: 4820

European-Finnish (FIN) AF: 0.768 AC: 8121 AN: 10574

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49213 AN: 67994

Other (OTH) AF: 0.744 AC: 1568 AN: 2108

Alfa AF: 0.742 Hom.: 59602

Bravo AF: 0.777

Asia WGS AF: 0.690 AC: 2399 AN: 3474

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	-0.86
CADD	Benign	0.76
DANN	Benign	0.84
PhyloP100		-0.74
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: rs2392209; hg19: chr7-33059407; COSMIC: COSV54239861; COSMIC: COSV54239861;