8-144095247-C-A

Variant names:

• chr8-144095247-C-A
• rs1361435658
• NM_001916.5:c.129+19C>A

Variant summary

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

The NM_001916.5(CYC1):​c.129+19C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000956 in 1,045,736 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: 32)
  • Exomes 𝑓: 9.6e-7 (0 hom.)
• Consequence: CYC1 NM_001916.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 0 publications found

Genes affected

CYC1 (HGNC:2579): (cytochrome c1) This gene encodes a subunit of the cytochrome bc1 complex, which plays an important role in the mitochondrial respiratory chain by transferring electrons from the Rieske iron-sulfur protein to cytochrome c. Mutations in this gene may cause mitochondrial complex III deficiency, nuclear type 6. [provided by RefSeq, Dec 2013]

CYC1 Gene-Disease associations (from GenCC):

• mitochondrial complex III deficiency nuclear type 6

  Inheritance: AR, Unknown Classification: DEFINITIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• mitochondrial complex III deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001916.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYC1	NM_001916.5	MANE Select	c.129+19C>A		intron	N/A	NP_001907.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYC1	ENST00000318911.5	TSL:1 MANE Select	c.129+19C>A		intron	N/A	ENSP00000317159.4	P08574
	CYC1	ENST00000533444.1	TSL:1	n.209C>A		non_coding_transcript_exon	Exon 1 of 6
	CYC1	ENST00000876792.1		c.129+19C>A		intron	N/A	ENSP00000546851.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.56e-7 AC: 1 AN: 1045736 Hom.: 0 Cov.: 32 AF XY: 0.00000203 AC XY: 1 AN XY: 493134

African (AFR) AF: 0.00 AC: 0 AN: 21724

American (AMR) AF: 0.00 AC: 0 AN: 7202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12618

East Asian (EAS) AF: 0.00 AC: 0 AN: 23186

South Asian (SAS) AF: 0.00 AC: 0 AN: 18994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2742

European-Non Finnish (NFE) AF: 0.00000111 AC: 1 AN: 898056

Other (OTH) AF: 0.00 AC: 0 AN: 41056

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.6
DANN	Benign	0.65
PhyloP100		-1.5
PromoterAI		-0.14	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1361435658; hg19: chr8-145150150;