rs974401612
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_003002.4(SDHD):c.21G>A(p.Leu7Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_003002.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SDHD | ENST00000375549.8 | c.21G>A | p.Leu7Leu | synonymous_variant | Exon 1 of 4 | 1 | NM_003002.4 | ENSP00000364699.3 | ||
ENSG00000255292 | ENST00000532699.1 | n.21G>A | non_coding_transcript_exon_variant | Exon 1 of 6 | 3 | ENSP00000456434.1 | ||||
TIMM8B | ENST00000504148.3 | c.-205C>T | upstream_gene_variant | 1 | NM_012459.4 | ENSP00000422122.2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152234Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461888Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727244
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74368
ClinVar
Submissions by phenotype
Pheochromocytoma;C1847319:Carney-Stratakis syndrome;C1868633:Paragangliomas with sensorineural hearing loss;CN166604:Cowden syndrome 3 Benign:1
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Hereditary cancer-predisposing syndrome Benign:1
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. -
Hereditary pheochromocytoma-paraganglioma Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at