6-158113439-GAGTGAATACCTGCTGA-CCTGTTGGT
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_032861.4(SERAC1):c.1822_1828+10delTCAGCAGGTATTCACTCinsACCAACAGG(p.Ser608fs) variant causes a frameshift, splice donor, splice region, synonymous, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. SAD608?) has been classified as Pathogenic. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_032861.4 frameshift, splice_donor, splice_region, synonymous, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SERAC1 | ENST00000647468.2 | c.1822_1828+10delTCAGCAGGTATTCACTCinsACCAACAGG | p.Ser608fs | frameshift_variant, splice_donor_variant, splice_region_variant, synonymous_variant, intron_variant | Exon 16 of 17 | NM_032861.4 | ENSP00000496731.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
not provided Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jun 24, 2024 | PP4, PM2, PM3_strong, PS4_moderate, PVS1_moderate - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Feb 27, 2025 | Canonical splice site variant predicted to result in an in-frame loss of the adjacent exon in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency or observed in the homozygous state in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 22683713, 27290639, 27331002, 37976411, 34751152, 37306826) - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Clinical Genetics Laboratory, Skane University Hospital Lund | May 27, 2022 | - - |
3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center | Nov 09, 2021 | PVS1, PM2 - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
SERAC1-related disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 07, 2022 | The SERAC1 c.1822_1828+10delinsACCAACAGG variant is predicted to result in an in-frame deletion and insertion. This variant is predicted to result in frameshift and premature protein termination, however as the deletion/insertion includes the exon 16/intron 16 boundary, this variant is also predicted to abolish the canonical splice donor site based on splicing prediction programs (Alamut Visual v2.11). This variant was reported in homozygous and compound heterozygous states in multiple individuals with 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (Wortmann et al. 2012. PubMed ID: 22683713; Pronicka et al. 2016. PubMed ID: 27290639). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as likely pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at