rs61755731
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_002156.5(HSPD1):c.425G>A(p.Arg142Lys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000242 in 1,614,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002156.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSPD1 | NM_002156.5 | c.425G>A | p.Arg142Lys | missense_variant, splice_region_variant | 3/12 | ENST00000388968.8 | |
HSPD1 | NM_199440.2 | c.425G>A | p.Arg142Lys | missense_variant, splice_region_variant | 3/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSPD1 | ENST00000388968.8 | c.425G>A | p.Arg142Lys | missense_variant, splice_region_variant | 3/12 | 1 | NM_002156.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00122 AC: 185AN: 152238Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000338 AC: 85AN: 251340Hom.: 0 AF XY: 0.000258 AC XY: 35AN XY: 135876
GnomAD4 exome AF: 0.000138 AC: 202AN: 1461796Hom.: 0 Cov.: 30 AF XY: 0.000125 AC XY: 91AN XY: 727202
GnomAD4 genome ? AF: 0.00123 AC: 188AN: 152356Hom.: 0 Cov.: 32 AF XY: 0.00113 AC XY: 84AN XY: 74516
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 07, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 15, 2022 | BS1 - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 07, 2018 | p.Arg142Lys (AGA>AAA): c.425 G>A in exon 3 of the HSPD1 gene (NM_002156.4). The R142K variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI Exome Sequencing Project reports R142K was observed in 25/4406 alleles from individuals of African American background. The R142K variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in MITONUC-MITOP panel(s). - |
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at