rs104894029

Positions:

• chr7-33015741-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_001002010.5(NT5C3A):​c.823G>C​(p.Gly275Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/20 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NT5C3A NM_001002010.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.73

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.983
• PP5: Variant 7-33015741-C-G is Pathogenic according to our data. Variant chr7-33015741-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 4488.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NT5C3A	NM_001002010.5	c.823G>C	p.Gly275Arg	missense_variant	8/9	ENST00000610140.7	NP_001002010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NT5C3A	ENST00000610140.7	c.823G>C	p.Gly275Arg	missense_variant	8/9	1	NM_001002010.5	ENSP00000476480	P3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2 AN: 1459708 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726366

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hemolytic anemia due to pyrimidine 5' nucleotidase deficiency Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 01, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.47
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.81	D;.;.;D;.;D;.;.
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	.;D;D;D;.;D;.;.
M_CAP	Pathogenic	0.33	D
MetaRNN	Pathogenic	0.98	D;D;D;D;D;D;D;D
MetaSVM	Pathogenic	0.98	D
MutationAssessor	Pathogenic	3.0	.;.;.;M;.;.;.;.
MutationTaster	Benign	1.0	A;A;A;A;A;A
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-6.8	.;D;D;.;.;.;D;D
REVEL	Pathogenic	0.93
Sift	Uncertain	0.0010	.;D;D;.;.;.;D;D
Sift4G	Pathogenic	0.0010	.;D;D;D;.;D;D;D
Polyphen		1.0	.;.;D;D;D;.;D;.
Vest4		0.98, 0.99, 0.99
MutPred		0.94		.;.;.;Gain of solvent accessibility (P = 0.0584);.;.;.;.;
MVP		0.98
MPC		0.85
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.94
gMVP		0.93

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

Publications

LitVar

Other links and lift over

dbSNP: rs104894029; hg19: chr7-33055353;