7-33014750-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 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

1
4
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.07
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2833431).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NT5C3ANM_001002010.5 linkc.976A>C p.Ile326Leu missense_variant Exon 9 of 9 ENST00000610140.7 NP_001002010.2 Q9H0P0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NT5C3AENST00000610140.7 linkc.976A>C p.Ile326Leu missense_variant Exon 9 of 9 1 NM_001002010.5 ENSP00000476480.2 X6RM59

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.070
D
BayesDel_noAF
Benign
-0.14
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.30
T;.;.;T;.;T;.;.
Eigen
Benign
-0.0059
Eigen_PC
Benign
0.17
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.58
.;T;T;T;.;T;.;.
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.28
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.42
T
MutationAssessor
Benign
1.3
.;.;.;L;.;.;.;.
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-1.0
.;N;N;.;.;.;N;N
REVEL
Uncertain
0.34
Sift
Benign
0.34
.;T;T;.;.;.;T;T
Sift4G
Benign
0.65
.;T;T;T;.;T;T;T
Polyphen
0.085, 0.10
.;.;B;B;B;.;B;.
Vest4
0.35, 0.41, 0.36, 0.41, 0.48
MutPred
0.59
.;.;.;Loss of catalytic residue at L336 (P = 0.0648);.;.;.;.;
MVP
0.76
MPC
0.25
ClinPred
0.53
D
GERP RS
5.9
Varity_R
0.44
gMVP
0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs563703074; hg19: chr7-33054362; API