rs1131690799
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1_ModeratePM2PP3_StrongPP5
The NM_032861.4(SERAC1):c.1403+1G>C variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Consequence
NM_032861.4 splice_donor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERAC1 | NM_032861.4 | c.1403+1G>C | splice_donor_variant | ENST00000647468.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERAC1 | ENST00000647468.2 | c.1403+1G>C | splice_donor_variant | NM_032861.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251072Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135686
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461712Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727160
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74380
ClinVar
Submissions by phenotype
3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome Pathogenic:3
Pathogenic, no assertion criteria provided | literature only | Yale Center for Mendelian Genomics, Yale University | Jul 10, 2014 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2006 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics | Jan 31, 2017 | The observed variant is not reported in 1000 genomes and ExAC databases and is likely to be pathogenic by online software like Mutation taster. A child born to consangeneous parents, normal up to one month, developed jaundice thereafter suspected with metabolic liver disease and died at 2 yrs of age. Parents were found to be heterozygous for mutation c.1403+1G>C in intron 13 of SERAC1 gene - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at