chr22-26477019-T-C
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_022081.6(HPS4):āc.250A>Gā(p.Ile84Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00405 in 1,614,220 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I84L) has been classified as Uncertain significance.
Frequency
Consequence
NM_022081.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HPS4 | NM_022081.6 | c.250A>G | p.Ile84Val | missense_variant | 4/14 | ENST00000398145.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HPS4 | ENST00000398145.7 | c.250A>G | p.Ile84Val | missense_variant | 4/14 | 1 | NM_022081.6 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00343 AC: 522AN: 152248Hom.: 3 Cov.: 32
GnomAD3 exomes AF: 0.00471 AC: 1184AN: 251464Hom.: 5 AF XY: 0.00508 AC XY: 691AN XY: 135900
GnomAD4 exome AF: 0.00412 AC: 6016AN: 1461854Hom.: 35 Cov.: 31 AF XY: 0.00436 AC XY: 3170AN XY: 727236
GnomAD4 genome AF: 0.00343 AC: 522AN: 152366Hom.: 3 Cov.: 32 AF XY: 0.00361 AC XY: 269AN XY: 74508
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:4
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 09, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 07, 2016 | p.Ile84Val in exon 4 of HPS4: This variant is not expected to have clinical sign ificance because it has been identified in 0.6% (400/66734) of European chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP rs149830675). - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 12, 2016 | - - |
Hermansky-Pudlak syndrome 4 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Jun 22, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Johns Hopkins Genomics, Johns Hopkins University | Mar 29, 2021 | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Hermansky-Pudlak syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at