Genetic Variant NT5C3A:p.Ile326Leu (chr7-33014750-T-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001002010.5(NT5C3A):c.976A>C(p.Ile326Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I326V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

NT5C3A
NM_001002010.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.07

Publications

0 publications found

Variant links:

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

NT5C3A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2833431).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NT5C3A	NM_001002010.5	MANE Select	c.976A>C	p.Ile326Leu	missense	Exon 9 of 9	NP_001002010.2	X6RM59
NT5C3A	NM_001374335.1		c.877A>C	p.Ile293Leu	missense	Exon 8 of 8	NP_001361264.1
NT5C3A	NM_001002009.3		c.874A>C	p.Ile292Leu	missense	Exon 10 of 10	NP_001002009.1	Q9H0P0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NT5C3A	ENST00000610140.7	TSL:1 MANE Select	c.976A>C	p.Ile326Leu	missense	Exon 9 of 9	ENSP00000476480.2	X6RM59
NT5C3A	ENST00000456458.5	TSL:1	n.*881A>C		non_coding_transcript_exon	Exon 10 of 10	ENSP00000389676.2	F8WDR0
NT5C3A	ENST00000456458.5	TSL:1	n.*881A>C		3_prime_UTR	Exon 10 of 10	ENSP00000389676.2	F8WDR0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.070

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.30

Eigen

Benign

-0.0059

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.58

M_CAP

Benign

0.041

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.42

MutationAssessor

Benign

1.3

PhyloP100

2.1

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.0

REVEL

Uncertain

0.34

Sift

Benign

0.34

Sift4G

Benign

0.65

Polyphen

0.085

Vest4

0.35

MutPred

0.59

Loss of catalytic residue at L336 (P = 0.0648)

MVP

0.76

MPC

0.25

ClinPred

0.53

GERP RS

5.9

Varity_R

0.44

gMVP

0.74

Mutation Taster

=54/46

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over