rs587598397
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP3BP6BS1BS2
The NM_003172.4(SURF1):c.54+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.004 in 1,390,498 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0029 ( 5 hom., cov: 34)
Exomes 𝑓: 0.0041 ( 14 hom. )
Consequence
SURF1
NM_003172.4 intron
NM_003172.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.389
Genes affected
SURF1 (HGNC:11474): (SURF1 cytochrome c oxidase assembly factor) This gene encodes a protein localized to the inner mitochondrial membrane and thought to be involved in the biogenesis of the cytochrome c oxidase complex. The protein is a member of the SURF1 family, which includes the related yeast protein SHY1 and rickettsial protein RP733. The gene is located in the surfeit gene cluster, a group of very tightly linked genes that do not share sequence similarity, where it shares a bidirectional promoter with SURF2 on the opposite strand. Defects in this gene are a cause of Leigh syndrome, a severe neurological disorder that is commonly associated with systemic cytochrome c oxidase deficiency. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
BP6
?
Variant 9-133356390-C-T is Benign according to our data. Variant chr9-133356390-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 139379.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=2, Likely_benign=2}. Variant chr9-133356390-C-T is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00285 (433/151860) while in subpopulation SAS AF= 0.00455 (22/4834). AF 95% confidence interval is 0.00383. There are 5 homozygotes in gnomad4. There are 206 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SURF1 | NM_003172.4 | c.54+10G>A | intron_variant | ENST00000371974.8 | |||
SURF1 | NM_001280787.1 | c.-222+10G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SURF1 | ENST00000371974.8 | c.54+10G>A | intron_variant | 1 | NM_003172.4 | P1 | |||
SURF1 | ENST00000615505.4 | c.-222+10G>A | intron_variant | 1 | |||||
SURF1 | ENST00000463965.1 | n.277+10G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00285 AC: 433AN: 151754Hom.: 5 Cov.: 34
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GnomAD3 exomes AF: 0.00535 AC: 127AN: 23718Hom.: 2 AF XY: 0.00554 AC XY: 80AN XY: 14446
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GnomAD4 exome AF: 0.00414 AC: 5127AN: 1238638Hom.: 14 Cov.: 36 AF XY: 0.00411 AC XY: 2493AN XY: 607026
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GnomAD4 genome ? AF: 0.00285 AC: 433AN: 151860Hom.: 5 Cov.: 34 AF XY: 0.00277 AC XY: 206AN XY: 74242
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 02, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 21, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | SURF1: BS2 - |
Leigh syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 01, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at