17-10681157-T-C
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_004589.4(SCO1):āc.868A>Gā(p.Ile290Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000782 in 1,614,190 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004589.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCO1 | NM_004589.4 | c.868A>G | p.Ile290Val | missense_variant | 6/6 | ENST00000255390.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCO1 | ENST00000255390.10 | c.868A>G | p.Ile290Val | missense_variant | 6/6 | 1 | NM_004589.4 | P1 | |
ENST00000584139.1 | n.117+307T>C | intron_variant, non_coding_transcript_variant | 3 | ||||||
SCO1 | ENST00000577427.1 | c.775A>G | p.Ile259Val | missense_variant | 6/6 | 3 | |||
SCO1 | ENST00000577335.2 | c.*690A>G | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000618 AC: 94AN: 152196Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000620 AC: 156AN: 251478Hom.: 0 AF XY: 0.000758 AC XY: 103AN XY: 135912
GnomAD4 exome AF: 0.000799 AC: 1168AN: 1461876Hom.: 3 Cov.: 31 AF XY: 0.000847 AC XY: 616AN XY: 727242
GnomAD4 genome ? AF: 0.000617 AC: 94AN: 152314Hom.: 0 Cov.: 33 AF XY: 0.000564 AC XY: 42AN XY: 74486
ClinVar
Submissions by phenotype
Mitochondrial complex 4 deficiency, nuclear type 4 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Apr 02, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 14, 2022 | - - |
Mitochondrial complex IV deficiency, nuclear type 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Leigh syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at