chr17-10680397-G-C

Position:

• chr17-10680397-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.886

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]

ACMG classification

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
SCO1	NM_004589.4	c.*722C>G		3_prime_UTR_variant	6/6	ENST00000255390.10	NP_004580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCO1	ENST00000255390.10	c.*722C>G		3_prime_UTR_variant	6/6	1	NM_004589.4	ENSP00000255390	P1
SCO1	ENST00000577427.1	c.*722C>G		3_prime_UTR_variant	6/6	3		ENSP00000463387
SCO1	ENST00000577335.2	c.*1450C>G		3_prime_UTR_variant, NMD_transcript_variant	7/7	3		ENSP00000464032

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70109 AN: 151834 Hom.: 16422 Cov.: 32

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.: 0 AF XY: 0.363 AC XY: 384 AN XY: 1058

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.: 32 AF XY: 0.461 AC XY: 34220 AN XY: 74254

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:4

Revision: criteria provided, multiple submitters, no conflicts

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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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

Other links and lift over

dbSNP: rs7512; hg19: chr17-10583714; COSMIC: COSV55136189; COSMIC: COSV55136189;