rs11974256

Variant names:

• chr7-33022213-C-T
• rs11974256
• NM_001002010.5:c.308-114G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001002010.5(NT5C3A):​c.308-114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0309 in 671,232 control chromosomes in the GnomAD database, including 728 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.028 (91 hom., cov: 33)
  • Exomes 𝑓: 0.032 (637 hom.)
• Consequence: NT5C3A NM_001002010.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.112 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.308-114G>A		intron	N/A	NP_001002010.2	X6RM59
	NT5C3A	NM_001374335.1		c.209-114G>A		intron	N/A	NP_001361264.1
	NT5C3A	NM_001002009.3		c.206-114G>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.308-114G>A		intron	N/A	ENSP00000476480.2	X6RM59
	NT5C3A	ENST00000456458.5	TSL:1	n.*213-114G>A		intron	N/A	ENSP00000389676.2	F8WDR0
	NT5C3A	ENST00000930183.1		c.308-114G>A		intron	N/A	ENSP00000600242.1

Frequencies

GnomAD3 genomes AF: 0.0284 AC: 4328 AN: 152160 Hom.: 93 Cov.: 33

Gnomad AFR AF: 0.0385

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.0185

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.00744

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0202

Gnomad OTH AF: 0.0335

GnomAD4 exome AF: 0.0316 AC: 16414 AN: 518954 Hom.: 637 AF XY: 0.0372 AC XY: 10442 AN XY: 281026

African (AFR) AF: 0.0382 AC: 559 AN: 14650

American (AMR) AF: 0.0142 AC: 432 AN: 30386

Ashkenazi Jewish (ASJ) AF: 0.0410 AC: 734 AN: 17886

East Asian (EAS) AF: 0.00817 AC: 256 AN: 31332

South Asian (SAS) AF: 0.122 AC: 7053 AN: 57646

European-Finnish (FIN) AF: 0.00845 AC: 282 AN: 33378

Middle Eastern (MID) AF: 0.0515 AC: 115 AN: 2234

European-Non Finnish (NFE) AF: 0.0198 AC: 6003 AN: 302886

Other (OTH) AF: 0.0343 AC: 980 AN: 28556

GnomAD4 genome AF: 0.0284 AC: 4330 AN: 152278 Hom.: 91 Cov.: 33 AF XY: 0.0289 AC XY: 2149 AN XY: 74470

African (AFR) AF: 0.0384 AC: 1595 AN: 41568

American (AMR) AF: 0.0230 AC: 351 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3472

East Asian (EAS) AF: 0.0185 AC: 96 AN: 5184

South Asian (SAS) AF: 0.120 AC: 581 AN: 4828

European-Finnish (FIN) AF: 0.00744 AC: 79 AN: 10612

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0202 AC: 1376 AN: 68002

Other (OTH) AF: 0.0360 AC: 76 AN: 2114

Alfa AF: 0.0236 Hom.: 6

Bravo AF: 0.0274

Asia WGS AF: 0.0630 AC: 218 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.48
PhyloP100		0.65
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11974256; hg19: chr7-33061825;