rs747214551
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_000414.4(HSD17B4):c.109G>A(p.Val37Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,596,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 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. V37F) has been classified as Uncertain significance.
Frequency
Consequence
NM_000414.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSD17B4 | NM_000414.4 | c.109G>A | p.Val37Ile | missense_variant | 2/24 | ENST00000510025.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSD17B4 | ENST00000510025.7 | c.109G>A | p.Val37Ile | missense_variant | 2/24 | 2 | NM_000414.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251440Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135896
GnomAD4 exome AF: 0.0000139 AC: 20AN: 1443862Hom.: 0 Cov.: 26 AF XY: 0.0000181 AC XY: 13AN XY: 719444
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74366
ClinVar
Submissions by phenotype
Bifunctional peroxisomal enzyme deficiency Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 12, 2016 | Variant classified as Uncertain Significance - Favor Benign. The p.Cys40Tyr vari ant in HSD17B4 has not been previously reported in individuals with hearing loss , but has been identified in 5/8652 of East Asian chromosome chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs7472 14551). Cysteine (Cys) at position 40 is not conserved in mammals or evolutionar ily distant species and 4 mammals (all rodent species: naked mole rat, guinea pi g, chinchilla, and bush-tailed rat) carry a tyrosine (Tyr), supporting that this change may be tolerated. Additional computational prediction tools suggest tha t the p.Cys40Tyr variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the p.Cys40Tyr variant is uncertain, these data suggest that it is more likely to be benign. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 27, 2018 | - - |
Bifunctional peroxisomal enzyme deficiency;C0685838:Perrault syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at