chr5-218252-G-GCGCAGGCGCGGTATCCCCCCTCCCCCGCCAGC

Variant names:

• chr5-218252-G-GCGCAGGCGCGGTATCCCCCCTCCCCCGCCAGC
• NM_004168.4:c.-104_-103insCGCAGGCGCGGTATCCCCCCTCCCCCGCCAGC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004168.4(SDHA):​c.-104_-103insCGCAGGCGCGGTATCCCCCCTCCCCCGCCAGC variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 36)
• Consequence: SDHA NM_004168.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 0 publications found

Genes affected

SDHA (HGNC:10680): (succinate dehydrogenase complex flavoprotein subunit A) This gene encodes a major catalytic subunit of succinate-ubiquinone oxidoreductase, a complex of the mitochondrial respiratory chain. The complex is composed of four nuclear-encoded subunits and is localized in the mitochondrial inner membrane. Mutations in this gene have been associated with a form of mitochondrial respiratory chain deficiency known as Leigh Syndrome. A pseudogene has been identified on chromosome 3q29. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

CCDC127 (HGNC:30520): (coiled-coil domain containing 127) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286001 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDHA	NM_004168.4	c.-104_-103insCGCAGGCGCGGTATCCCCCCTCCCCCGCCAGC		upstream_gene_variant		ENST00000264932.11	NP_004159.2
CCDC127	NM_145265.3	c.-171_-170insGCTGGCGGGGGAGGGGGGATACCGCGCCTGCG		upstream_gene_variant		ENST00000296824.4	NP_660308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDHA	ENST00000264932.11	c.-104_-103insCGCAGGCGCGGTATCCCCCCTCCCCCGCCAGC		upstream_gene_variant		1	NM_004168.4	ENSP00000264932.6
CCDC127	ENST00000296824.4	c.-171_-170insGCTGGCGGGGGAGGGGGGATACCGCGCCTGCG		upstream_gene_variant		1	NM_145265.3	ENSP00000296824.2
ENSG00000286001	ENST00000651543.1	n.-104_-103insCGCAGGCGCGGTATCCCCCCTCCCCCGCCAGC		upstream_gene_variant				ENSP00000499215.1

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr5-218367;