chr11-75566785-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001235.5(SERPINH1):āc.436T>Cā(p.Phe146Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. F146F) has been classified as Likely benign.
Frequency
Consequence
NM_001235.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINH1 | NM_001235.5 | c.436T>C | p.Phe146Leu | missense_variant | 2/5 | ENST00000358171.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINH1 | ENST00000358171.8 | c.436T>C | p.Phe146Leu | missense_variant | 2/5 | 1 | NM_001235.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152236Hom.: 0 Cov.: 34
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460910Hom.: 0 Cov.: 70 AF XY: 0.00 AC XY: 0AN XY: 726820
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152236Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74374
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 22, 2023 | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 146 of the SERPINH1 protein (p.Phe146Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of osteogenesis imperfecta (Invitae). ClinVar contains an entry for this variant (Variation ID: 591550). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SERPINH1 protein function. 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. - |
Uncertain significance, no assertion criteria provided | research | Gharavi Laboratory, Columbia University | Sep 16, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at