ENST00000651543.1:n.-6G>A

Variant names:

• chr5-218292-C-A
• rs1161250379
• NM_004168.4:c.-64C>A

Variant summary

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

The ENST00000651543.1(ENSG00000286001):​n.-64C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000786 in 1,272,910 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: 7.9e-7 (0 hom.)
• Consequence: ENSG00000286001 ENST00000651543.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• 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=-0.7).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDHA	NM_004168.4	c.-64C>A		upstream_gene_variant		ENST00000264932.11	NP_004159.2
CCDC127	NM_145265.3	c.-210G>T		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.-64C>A		upstream_gene_variant		1	NM_004168.4	ENSP00000264932.6
CCDC127	ENST00000296824.4	c.-210G>T		upstream_gene_variant		1	NM_145265.3	ENSP00000296824.2
ENSG00000286001	ENST00000651543.1	n.-64C>A		upstream_gene_variant				ENSP00000499215.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.86e-7 AC: 1 AN: 1272910 Hom.: 0 Cov.: 27 AF XY: 0.00000160 AC XY: 1 AN XY: 625768

African (AFR) AF: 0.0000389 AC: 1 AN: 25690

American (AMR) AF: 0.00 AC: 0 AN: 19328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20210

East Asian (EAS) AF: 0.00 AC: 0 AN: 29450

South Asian (SAS) AF: 0.00 AC: 0 AN: 62818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3602

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1027442

Other (OTH) AF: 0.00 AC: 0 AN: 51998

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.2
DANN	Benign	0.55
PhyloP100		-1.2
PromoterAI		-0.24	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1161250379; hg19: chr5-218407;