Variant 17-10680397-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004589.4(SCO1):c.*722C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 154,044 control chromosomes in the GnomAD database, including 16,598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.46 ( 16435 hom., cov: 32)

Exomes 𝑓: 0.37 ( 163 hom. )

Consequence

SCO1
NM_004589.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: -0.886

Variant links:

Genes affected

SCO1 (HGNC:10603): (synthesis of cytochrome C oxidase 1) Mammalian cytochrome c oxidase (COX) catalyzes the transfer of reducing equivalents from cytochrome c to molecular oxygen and pumps protons across the inner mitochondrial membrane. In yeast, 2 related COX assembly genes, SCO1 and SCO2 (synthesis of cytochrome c oxidase), enable subunits 1 and 2 to be incorporated into the holoprotein. This gene is the human homolog to the yeast SCO1 gene. [provided by RefSeq, Jul 2008]

SCO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-10680397-G-C is Benign according to our data. Variant chr17-10680397-G-C is described in ClinVar as [Benign]. Clinvar id is 321780.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCO1	NM_004589.4 linkuse as main transcript	c.*722C>G		3_prime_UTR_variant	6/6	ENST00000255390.10

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
SCO1	ENST00000255390.10 linkuse as main transcript	c.*722C>G	3_prime_UTR_variant	6/6	1	NM_004589.4	P1
SCO1	ENST00000577427.1 linkuse as main transcript	c.*722C>G	3_prime_UTR_variant	6/6	3
SCO1	ENST00000577335.2 linkuse as main transcript	c.*1450C>G	3_prime_UTR_variant, NMD_transcript_variant	7/7	3

Frequencies

GnomAD3 genomes

AF:

0.462

AC:

70109

AN:

151834

Hom.:

16422

Cov.:

show subpopulations

Gnomad AFR

AF:

0.503

Gnomad AMI

AF:

0.439

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.528

Gnomad EAS

AF:

0.542

Gnomad SAS

AF:

0.361

Gnomad FIN

AF:

0.440

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.434

Gnomad OTH

AF:

0.479

GnomAD4 exome

AF:

0.370

AC:

774

AN:

2092

Hom.:

163

Cov.:

AF XY:

0.363

AC XY:

384

AN XY:

1058

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.413

Gnomad4 ASJ exome

AF:

0.250

Gnomad4 EAS exome

AF:

0.400

Gnomad4 SAS exome

AF:

0.244

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.376

Gnomad4 OTH exome

AF:

0.300

GnomAD4 genome

AF:

0.462

AC:

70171

AN:

151952

Hom.:

16435

Cov.:

AF XY:

0.461

AC XY:

34220

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.502

Gnomad4 AMR

AF:

0.479

Gnomad4 ASJ

AF:

0.528

Gnomad4 EAS

AF:

0.542

Gnomad4 SAS

AF:

0.362

Gnomad4 FIN

AF:

0.440

Gnomad4 NFE

AF:

0.434

Gnomad4 OTH

AF:

0.485

Alfa

AF:

0.452

Hom.:

2073

Bravo

AF:

0.469

Asia WGS

AF:

0.482

AC:

1676

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Mitochondrial complex IV deficiency, nuclear type 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Leigh syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.39

DANN

Benign

0.55

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