7-97853071-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000394308.8(ASNS):c.1465G>A(p.Val489Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000237 in 1,579,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V489F) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000394308.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ASNS | NM_001673.5 | c.1465G>A | p.Val489Ile | missense_variant | 12/13 | ENST00000394308.8 | NP_001664.3 | |
CZ1P-ASNS | NR_147989.1 | n.3168G>A | non_coding_transcript_exon_variant | 18/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ASNS | ENST00000394308.8 | c.1465G>A | p.Val489Ile | missense_variant | 12/13 | 1 | NM_001673.5 | ENSP00000377845 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000107 AC: 24AN: 224098Hom.: 0 AF XY: 0.000107 AC XY: 13AN XY: 121084
GnomAD4 exome AF: 0.000249 AC: 355AN: 1427102Hom.: 0 Cov.: 31 AF XY: 0.000237 AC XY: 168AN XY: 707580
GnomAD4 genome AF: 0.000131 AC: 20AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74336
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 09, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 13, 2022 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 489 of the ASNS protein (p.Val489Ile). This variant is present in population databases (rs772079299, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ASNS-related conditions. ClinVar contains an entry for this variant (Variation ID: 445433). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ASNS protein function. 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. - |
Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 24, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 13, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at