Genetic Variant NM_001002010.5:c.988A>G (chr7-33014738-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001002010.5(NT5C3A):c.988A>G(p.Ile330Val) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I330M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

NT5C3A
NM_001002010.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24806139).

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.988A>G	p.Ile330Val	missense	Exon 9 of 9	NP_001002010.2	X6RM59
NT5C3A	NM_001374335.1		c.889A>G	p.Ile297Val	missense	Exon 8 of 8	NP_001361264.1
NT5C3A	NM_001002009.3		c.886A>G	p.Ile296Val	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.988A>G	p.Ile330Val	missense	Exon 9 of 9	ENSP00000476480.2	X6RM59
NT5C3A	ENST00000456458.5	TSL:1	n.*893A>G		non_coding_transcript_exon	Exon 10 of 10	ENSP00000389676.2	F8WDR0
NT5C3A	ENST00000456458.5	TSL:1	n.*893A>G		3_prime_UTR	Exon 10 of 10	ENSP00000389676.2	F8WDR0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.31

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.059

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.78

M_CAP

Benign

0.034

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.46

MutationAssessor

Benign

1.2

PhyloP100

2.3

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.44

REVEL

Uncertain

0.29

Sift

Benign

0.26

Sift4G

Benign

0.17

Polyphen

0.0

Vest4

0.088

MutPred

0.73

Gain of methylation at K334 (P = 0.0499)

MVP

0.75

MPC

0.20

ClinPred

0.29

GERP RS

3.3

Varity_R

0.085

gMVP

0.54

Mutation Taster

=66/34

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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