5-218308-C-CGCAGTCTGCGCAGGGACTGGCGGGACTGCGCG

Variant names:

• chr5-218308-C-CGCAGTCTGCGCAGGGACTGGCGGGACTGCGCG
• ENST00000651543.1:n.-45_-14dupAGTCTGCGCAGGGACTGGCGGGACTGCGCGGC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The ENST00000651543.1(ENSG00000286001):​n.-45_-14dupAGTCTGCGCAGGGACTGGCGGGACTGCGCGGC variant causes a non coding transcript exon 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. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ENSG00000286001 ENST00000651543.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.41
• Publications: 0 publications found

Genes affected

ENSG00000286001 (HGNC:):

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 5-218308-C-CGCAGTCTGCGCAGGGACTGGCGGGACTGCGCG is Benign according to our data. Variant chr5-218308-C-CGCAGTCTGCGCAGGGACTGGCGGGACTGCGCG is described in ClinVar as [Benign]. Clinvar id is 3904662.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDHA	NM_004168.4	c.-48_-47insGCAGTCTGCGCAGGGACTGGCGGGACTGCGCG		upstream_gene_variant		ENST00000264932.11	NP_004159.2
CCDC127	NM_145265.3	c.-227_-226insCGCGCAGTCCCGCCAGTCCCTGCGCAGACTGC		upstream_gene_variant		ENST00000296824.4	NP_660308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286001	ENST00000651543.1	n.-45_-14dupAGTCTGCGCAGGGACTGGCGGGACTGCGCGGC		non_coding_transcript_exon_variant	Exon 1 of 24			ENSP00000499215.1
SDHA	ENST00000264932.11	c.-45_-14dupAGTCTGCGCAGGGACTGGCGGGACTGCGCGGC		5_prime_UTR_variant	Exon 1 of 15	1	NM_004168.4	ENSP00000264932.6
ENSG00000286001	ENST00000651543.1	n.-45_-14dupAGTCTGCGCAGGGACTGGCGGGACTGCGCGGC		5_prime_UTR_variant	Exon 1 of 24			ENSP00000499215.1
SDHA	ENST00000264932.11	c.-48_-47insGCAGTCTGCGCAGGGACTGGCGGGACTGCGCG		upstream_gene_variant		1	NM_004168.4	ENSP00000264932.6
CCDC127	ENST00000296824.4	c.-258_-227dupCGCGCAGTCCCGCCAGTCCCTGCGCAGACTGC		upstream_gene_variant		1	NM_145265.3	ENSP00000296824.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Pheochromocytoma/paraganglioma syndrome 5 Benign:1

Feb 27, 2025

Myriad Genetics, Inc.

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4

Splicing

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

Other links and lift over

hg19: chr5-218423;