5-225529-C-T
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_004168.4(SDHA):c.423C>T(p.Tyr141Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000112 in 1,613,818 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_004168.4 synonymous
Scores
Clinical Significance
Conservation
Publications
- hereditary pheochromocytoma-paragangliomaInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- pheochromocytoma/paraganglioma syndrome 5Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- mitochondrial complex II deficiency, nuclear type 1Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
- neurodegeneration with ataxia and late-onset optic atrophyInheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- Leigh syndromeInheritance: AR Classification: MODERATE Submitted by: Ambry Genetics, ClinGen
- familial isolated dilated cardiomyopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- gastrointestinal stromal tumorInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Leigh syndrome with leukodystrophyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- mitochondrial complex II deficiencyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- dilated cardiomyopathy 1GGInheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
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ACMG classification
Our verdict: Benign. The variant received -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SDHA | NM_004168.4 | c.423C>T | p.Tyr141Tyr | synonymous_variant | Exon 4 of 15 | ENST00000264932.11 | NP_004159.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SDHA | ENST00000264932.11 | c.423C>T | p.Tyr141Tyr | synonymous_variant | Exon 4 of 15 | 1 | NM_004168.4 | ENSP00000264932.6 | ||
ENSG00000286001 | ENST00000651543.1 | n.423C>T | non_coding_transcript_exon_variant | Exon 4 of 24 | ENSP00000499215.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152166Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00000399 AC: 1AN: 250568 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461652Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 727134 show subpopulations
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74338 show subpopulations
ClinVar
Submissions by phenotype
Pheochromocytoma/paraganglioma syndrome 5 Benign:1
This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -
Pheochromocytoma/paraganglioma syndrome 5;C5700310:Mitochondrial complex II deficiency, nuclear type 1 Benign:1
- -
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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at