rs58548334
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000195.5(HPS1):āc.11T>Cā(p.Val4Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.026 in 1,613,178 control chromosomes in the GnomAD database, including 791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V4I) has been classified as Uncertain significance.
Frequency
Consequence
NM_000195.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HPS1 | NM_000195.5 | c.11T>C | p.Val4Ala | missense_variant | 3/20 | ENST00000361490.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HPS1 | ENST00000361490.9 | c.11T>C | p.Val4Ala | missense_variant | 3/20 | 1 | NM_000195.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0362 AC: 5507AN: 151990Hom.: 124 Cov.: 32
GnomAD3 exomes AF: 0.0313 AC: 7864AN: 251482Hom.: 175 AF XY: 0.0323 AC XY: 4390AN XY: 135912
GnomAD4 exome AF: 0.0249 AC: 36452AN: 1461070Hom.: 667 Cov.: 30 AF XY: 0.0258 AC XY: 18749AN XY: 726898
GnomAD4 genome ? AF: 0.0363 AC: 5516AN: 152108Hom.: 124 Cov.: 32 AF XY: 0.0376 AC XY: 2797AN XY: 74372
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Val4Ala in exon 3 of HPS1: This variant is not expected to have clinical signifi cance because it has been identified in 6.3% (277/4406) of African American chro mosomes from a broad population by the NHLBI Exome Sequencing Project (http://ev s.gs.washington.edu/EVS; dbSNP rs58548334). - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 20, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Hermansky-Pudlak syndrome Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Feb 26, 2021 | - - |
Hermansky-Pudlak syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at