rs782125974
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_003172.4(SURF1):c.185T>G(p.Leu62Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000229 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. L62I) has been classified as Uncertain significance.
Frequency
Consequence
NM_003172.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SURF1 | NM_003172.4 | c.185T>G | p.Leu62Arg | missense_variant | 3/9 | ENST00000371974.8 | |
SURF1 | NM_001280787.1 | c.-143T>G | 5_prime_UTR_variant | 2/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SURF1 | ENST00000371974.8 | c.185T>G | p.Leu62Arg | missense_variant | 3/9 | 1 | NM_003172.4 | P1 | |
SURF1 | ENST00000615505.4 | c.-143T>G | 5_prime_UTR_variant | 2/8 | 1 | ||||
SURF1 | ENST00000437995.1 | n.131T>G | non_coding_transcript_exon_variant | 2/8 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251410Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135870
GnomAD4 exome AF: 0.0000239 AC: 35AN: 1461736Hom.: 0 Cov.: 32 AF XY: 0.0000220 AC XY: 16AN XY: 727174
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74360
ClinVar
Submissions by phenotype
Leigh syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 26, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 05, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 62 of the SURF1 protein (p.Leu62Arg). This variant is present in population databases (rs782125974, gnomAD 0.0009%). 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: 580531). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at