rs878853268
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The ENST00000210444.6(NANS):c.979_981dup(p.Ile327dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
NANS
ENST00000210444.6 inframe_insertion
ENST00000210444.6 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.153
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]
TRIM14 (HGNC:16283): (tripartite motif containing 14) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic bodies and its function has not been determined. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in ENST00000210444.6. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NANS | NM_018946.4 | c.979_981dup | p.Ile327dup | inframe_insertion | 6/6 | ENST00000210444.6 | NP_061819.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NANS | ENST00000210444.6 | c.979_981dup | p.Ile327dup | inframe_insertion | 6/6 | 1 | NM_018946.4 | ENSP00000210444 | P1 | |
TRIM14 | ENST00000375098.7 | c.*28+4489_*28+4490insATG | intron_variant | 2 | ENSP00000364239 | P1 | ||||
NANS | ENST00000461452.1 | n.2906_2908dup | non_coding_transcript_exon_variant | 4/4 | 2 | |||||
TRIM14 | ENST00000478530.1 | n.561-1692_561-1691insATG | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727248
GnomAD4 exome
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1461892
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31
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727248
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spondyloepimetaphyseal dysplasia, Genevieve type Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 20, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 23, 2021 | This variant has been observed in individual(s) with clinical features of Spondyloepimetaphyseal dysplasia, Camera-Genevieve type (PMID: 27213289). This variant is not present in population databases (gnomAD no frequency). This variant, c.979_981dup, results in the insertion of 1 amino acid(s) of the NANS protein (p.Ile327dup), but otherwise preserves the integrity of the reading frame. ClinVar contains an entry for this variant (Variation ID: 235189). 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
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Name
Calibrated prediction
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at