chr5-218296-G-C

Variant names:

• chr5-218296-G-C
• rs1734487125
• NM_004168.4:c.-60G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004168.4(SDHA):​c.-60G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000234 in 1,282,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: SDHA NM_004168.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDHA	NM_004168.4	c.-60G>C		upstream_gene_variant		ENST00000264932.11	NP_004159.2
CCDC127	NM_145265.3	c.-214C>G		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.-60G>C		upstream_gene_variant		1	NM_004168.4	ENSP00000264932.6
CCDC127	ENST00000296824.4	c.-214C>G		upstream_gene_variant		1	NM_145265.3	ENSP00000296824.2
ENSG00000286001	ENST00000651543.1	n.-60G>C		upstream_gene_variant				ENSP00000499215.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000234 AC: 3 AN: 1282468 Hom.: 0 Cov.: 28 AF XY: 0.00000475 AC XY: 3 AN XY: 630980

African (AFR) AF: 0.00 AC: 0 AN: 25948

American (AMR) AF: 0.00 AC: 0 AN: 20676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20454

East Asian (EAS) AF: 0.00 AC: 0 AN: 29920

South Asian (SAS) AF: 0.0000312 AC: 2 AN: 64080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3642

European-Non Finnish (NFE) AF: 9.68e-7 AC: 1 AN: 1032638

Other (OTH) AF: 0.00 AC: 0 AN: 52332

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.8
DANN	Benign	0.41
PhyloP100		-0.46
PromoterAI		-0.0066	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1734487125; hg19: chr5-218411;