chr2-219570271-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_015311.3(OBSL1):āc.962C>Gā(p.Ala321Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000244 in 1,600,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A321V) has been classified as Uncertain significance.
Frequency
Consequence
NM_015311.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OBSL1 | NM_015311.3 | c.962C>G | p.Ala321Gly | missense_variant | 1/21 | ENST00000404537.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OBSL1 | ENST00000404537.6 | c.962C>G | p.Ala321Gly | missense_variant | 1/21 | 1 | NM_015311.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152232Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000383 AC: 9AN: 235026Hom.: 0 AF XY: 0.0000467 AC XY: 6AN XY: 128390
GnomAD4 exome AF: 0.0000242 AC: 35AN: 1448210Hom.: 0 Cov.: 30 AF XY: 0.0000390 AC XY: 28AN XY: 718210
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74360
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 29, 2023 | The c.962C>G (p.A321G) alteration is located in exon 1 (coding exon 1) of the OBSL1 gene. This alteration results from a C to G substitution at nucleotide position 962, causing the alanine (A) at amino acid position 321 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 22, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 321 of the OBSL1 protein (p.Ala321Gly). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 2569102). This variant has not been reported in the literature in individuals affected with OBSL1-related conditions. This variant is present in population databases (rs750505464, gnomAD 0.03%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at