rs149424705
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_003900.5(SQSTM1):c.800G>A(p.Arg267His) variant causes a missense change. The variant allele was found at a frequency of 0.000096 in 1,614,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. R267C) has been classified as Uncertain significance.
Frequency
Consequence
NM_003900.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SQSTM1 | NM_003900.5 | c.800G>A | p.Arg267His | missense_variant | 6/8 | ENST00000389805.9 | |
SQSTM1 | NM_001142298.2 | c.548G>A | p.Arg183His | missense_variant | 7/9 | ||
SQSTM1 | NM_001142299.2 | c.548G>A | p.Arg183His | missense_variant | 7/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SQSTM1 | ENST00000389805.9 | c.800G>A | p.Arg267His | missense_variant | 6/8 | 1 | NM_003900.5 | P1 | |
SQSTM1 | ENST00000360718.5 | c.548G>A | p.Arg183His | missense_variant | 5/7 | 1 | |||
SQSTM1 | ENST00000510187.5 | c.800G>A | p.Arg267His | missense_variant | 6/7 | 5 | |||
SQSTM1 | ENST00000466342.1 | n.499G>A | non_coding_transcript_exon_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152174Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251446Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135906
GnomAD4 exome AF: 0.0000978 AC: 143AN: 1461886Hom.: 0 Cov.: 40 AF XY: 0.0000963 AC XY: 70AN XY: 727244
GnomAD4 genome AF: 0.0000788 AC: 12AN: 152292Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74476
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 14, 2022 | The c.800G>A (p.R267H) alteration is located in exon 6 (coding exon 6) of the SQSTM1 gene. This alteration results from a G to A substitution at nucleotide position 800, causing the arginine (R) at amino acid position 267 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Paget disease of bone 2, early-onset;C5779877:Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 03, 2023 | This variant is present in population databases (rs149424705, gnomAD 0.02%). 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. 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 SQSTM1 protein function. ClinVar contains an entry for this variant (Variation ID: 475405). This variant has not been reported in the literature in individuals affected with SQSTM1-related conditions. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 267 of the SQSTM1 protein (p.Arg267His). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at