rs148266178
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_013296.5(GPSM2):c.1670G>A(p.Arg557His) variant causes a missense change. The variant allele was found at a frequency of 0.000105 in 1,613,406 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R557C) has been classified as Likely benign.
Frequency
Consequence
NM_013296.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GPSM2 | NM_013296.5 | c.1670G>A | p.Arg557His | missense_variant | Exon 14 of 15 | ENST00000264126.9 | NP_037428.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 151988Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000916 AC: 23AN: 251138Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135726
GnomAD4 exome AF: 0.000103 AC: 150AN: 1461300Hom.: 0 Cov.: 31 AF XY: 0.000107 AC XY: 78AN XY: 726980
GnomAD4 genome AF: 0.000125 AC: 19AN: 152106Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74330
ClinVar
Submissions by phenotype
not specified Uncertain:1
The p.Arg557His variant in GPSM2 has not been previously reported in individuals with hearing loss, but has been identified in 4/16506 East Asian chromosomes an d 2/10372 African chromosomes by the Exome Aggregation Consortium (ExAC, http:// exac.broadinstitute.org; dbSNP rs148266178). Computational prediction tools and conservation analyses suggest that the variant may impact the protein, though th is information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Arg557His variant is uncertain. -
Inborn genetic diseases Uncertain:1
The c.1670G>A (p.R557H) alteration is located in exon 14 (coding exon 13) of the GPSM2 gene. This alteration results from a G to A substitution at nucleotide position 1670, causing the arginine (R) at amino acid position 557 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at