chr9-133352068-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_003172.4(SURF1):c.826G>A(p.Val276Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000993 in 1,611,532 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V276A) has been classified as Uncertain significance.
Frequency
Consequence
NM_003172.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SURF1 | NM_003172.4 | c.826G>A | p.Val276Met | missense_variant | 8/9 | ENST00000371974.8 | |
SURF1 | NM_001280787.1 | c.499G>A | p.Val167Met | missense_variant | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SURF1 | ENST00000371974.8 | c.826G>A | p.Val276Met | missense_variant | 8/9 | 1 | NM_003172.4 | P1 | |
SURF1 | ENST00000615505.4 | c.499G>A | p.Val167Met | missense_variant | 7/8 | 1 | |||
SURF1 | ENST00000437995.1 | n.736G>A | non_coding_transcript_exon_variant | 7/8 | 5 | ||||
SURF1 | ENST00000495952.5 | n.816G>A | non_coding_transcript_exon_variant | 4/5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152164Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000813 AC: 2AN: 245874Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133114
GnomAD4 exome AF: 0.00000891 AC: 13AN: 1459368Hom.: 0 Cov.: 33 AF XY: 0.00000965 AC XY: 7AN XY: 725680
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152164Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74334
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 13, 2016 | - - |
Leigh syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 23, 2022 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 276 of the SURF1 protein (p.Val276Met). This variant is present in population databases (rs141561701, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SURF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 521139). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 30, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at