11-112094808-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 6P and 10B. PM1PM2PM5BP4_ModerateBP6_Very_Strong
The ENST00000528048.5(SDHD):c.173C>T(p.Ala58Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A58S) has been classified as Likely pathogenic.
Frequency
Consequence
ENST00000528048.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SDHD | NM_003002.4 | c.318C>T | p.Gly106= | synonymous_variant | 4/4 | ENST00000375549.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SDHD | ENST00000375549.8 | c.318C>T | p.Gly106= | synonymous_variant | 4/4 | 1 | NM_003002.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250578Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135596
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459370Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 725992
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Pheochromocytoma;C1847319:Carney-Stratakis syndrome;C1868633:Paragangliomas with sensorineural hearing loss;CN166604:Cowden syndrome 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 04, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 22, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at