Variant 8-144095198-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001916.5(CYC1):c.99T>G(p.Arg33Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 1,205,102 control chromosomes in the GnomAD database, including 497,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 57859 hom., cov: 30)

Exomes 𝑓: 0.91 ( 439564 hom. )

Consequence

CYC1
NM_001916.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.968

Variant links:

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 links:

CYC1 (HGNC:):

CYC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 8-144095198-T-G is Benign according to our data. Variant chr8-144095198-T-G is described in ClinVar as [Benign]. Clinvar id is 379959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144095198-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.968 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYC1	NM_001916.5 linkuse as main transcript	c.99T>G	p.Arg33Arg	synonymous_variant	1/7	ENST00000318911.5	NP_001907.3	P08574

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYC1	ENST00000318911.5 linkuse as main transcript	c.99T>G	p.Arg33Arg	synonymous_variant	1/7	1	NM_001916.5	ENSP00000317159.4		P08574
CYC1	ENST00000533444.1 linkuse as main transcript	n.160T>G		non_coding_transcript_exon_variant	1/6	1

Frequencies

GnomAD3 genomes

AF:

0.870

AC:

131514

AN:

151248

Hom.:

57838

Cov.:

show subpopulations

Gnomad AFR

AF:

0.726

Gnomad AMI

AF:

0.943

Gnomad AMR

AF:

0.915

Gnomad ASJ

AF:

0.922

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.958

Gnomad FIN

AF:

0.928

Gnomad MID

AF:

0.885

Gnomad NFE

AF:

0.917

Gnomad OTH

AF:

0.882

GnomAD3 exomes

AF:

0.900

AC:

655

AN:

728

Hom.:

293

AF XY:

0.898

AC XY:

467

AN XY:

520

show subpopulations

Gnomad AFR exome

AF:

0.667

Gnomad AMR exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.919

Gnomad NFE exome

AF:

0.887

Gnomad OTH exome

AF:

0.857

GnomAD4 exome

AF:

0.913

AC:

961689

AN:

1053746

Hom.:

439564

Cov.:

AF XY:

0.914

AC XY:

454256

AN XY:

497264

show subpopulations

Gnomad4 AFR exome

AF:

0.701

Gnomad4 AMR exome

AF:

0.928

Gnomad4 ASJ exome

AF:

0.923

Gnomad4 EAS exome

AF:

0.997

Gnomad4 SAS exome

AF:

0.961

Gnomad4 FIN exome

AF:

0.925

Gnomad4 NFE exome

AF:

0.914

Gnomad4 OTH exome

AF:

0.909

GnomAD4 genome

AF:

0.869

AC:

131586

AN:

151356

Hom.:

57859

Cov.:

AF XY:

0.872

AC XY:

64549

AN XY:

73984

show subpopulations

Gnomad4 AFR

AF:

0.726

Gnomad4 AMR

AF:

0.915

Gnomad4 ASJ

AF:

0.922

Gnomad4 EAS

AF:

0.997

Gnomad4 SAS

AF:

0.958

Gnomad4 FIN

AF:

0.928

Gnomad4 NFE

AF:

0.917

Gnomad4 OTH

AF:

0.884

Alfa

AF:

0.902

Hom.:

3095

Bravo

AF:

0.861

Asia WGS

AF:

0.963

AC:

3299

AN:

3428

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 15, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 02, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Mitochondrial complex III deficiency nuclear type 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.79

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over