chr9-98056860-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018946.4(NANS):āc.52C>Gā(p.Pro18Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,612,262 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 34)
Exomes š: 0.000034 ( 0 hom. )
Consequence
NANS
NM_018946.4 missense
NM_018946.4 missense
Scores
4
9
6
Clinical Significance
Conservation
PhyloP100: 7.17
Genes affected
NANS (HGNC:19237): (N-acetylneuraminate synthase) This gene encodes an enzyme that functions in the biosynthetic pathways of sialic acids. In vitro, the encoded protein uses N-acetylmannosamine 6-phosphate and mannose 6-phosphate as substrates to generate phosphorylated forms of N-acetylneuraminic acid (Neu5Ac) and 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN), respectively; however, it exhibits much higher activity toward the Neu5Ac phosphate product. In insect cells, expression of this gene results in Neu5Ac and KDN production. This gene is related to the E. coli sialic acid synthase gene neuB, and it can partially restore sialic acid synthase activity in an E. coli neuB-negative mutant. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NANS | NM_018946.4 | c.52C>G | p.Pro18Ala | missense_variant | 1/6 | ENST00000210444.6 | NP_061819.2 | |
TRIM14 | XM_047424162.1 | c.*29-21047G>C | intron_variant | XP_047280118.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NANS | ENST00000210444.6 | c.52C>G | p.Pro18Ala | missense_variant | 1/6 | 1 | NM_018946.4 | ENSP00000210444 | P1 | |
NANS | ENST00000480925.1 | n.91C>G | non_coding_transcript_exon_variant | 1/2 | 2 | |||||
NANS | ENST00000495319.1 | n.93C>G | non_coding_transcript_exon_variant | 1/5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152238Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000773 AC: 19AN: 245836Hom.: 0 AF XY: 0.0000672 AC XY: 9AN XY: 133868
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GnomAD4 exome AF: 0.0000336 AC: 49AN: 1460024Hom.: 0 Cov.: 38 AF XY: 0.0000289 AC XY: 21AN XY: 726402
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152238Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74374
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 01, 2022 | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 18 of the NANS protein (p.Pro18Ala). This variant is present in population databases (rs368286579, gnomAD 0.09%). This variant has not been reported in the literature in individuals affected with NANS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at