17-10680847-A-G

Position:

• chr17-10680847-A-G

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.*272T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 506,918 control chromosomes in the GnomAD database, including 490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (375 hom., cov: 33)
  • Exomes 𝑓: 0.0071 (115 hom.)
• Consequence: SCO1 NM_004589.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.23

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-10680847-A-G is Benign according to our data. Variant chr17-10680847-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 321788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCO1	NM_004589.4	c.*272T>C		3_prime_UTR_variant	6/6	ENST00000255390.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCO1	ENST00000255390.10	c.*272T>C		3_prime_UTR_variant	6/6	1	NM_004589.4	P1
	ENST00000584139.1	n.114A>G		non_coding_transcript_exon_variant	1/2	3
SCO1	ENST00000577427.1	c.*272T>C		3_prime_UTR_variant	6/6	3
SCO1	ENST00000577335.2	c.*1000T>C		3_prime_UTR_variant, NMD_transcript_variant	7/7	3

Frequencies

GnomAD3 genomes AF: 0.0388 AC: 5899 AN: 152196 Hom.: 370 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0248

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.0349

GnomAD4 exome AF: 0.00712 AC: 2525 AN: 354604 Hom.: 115 Cov.: 3 AF XY: 0.00625 AC XY: 1181 AN XY: 188918

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.0104

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0206

Gnomad4 SAS exome AF: 0.00226

Gnomad4 FIN exome AF: 0.0000532

Gnomad4 NFE exome AF: 0.000427

Gnomad4 OTH exome AF: 0.0139

GnomAD4 genome AF: 0.0389 AC: 5930 AN: 152314 Hom.: 375 Cov.: 33 AF XY: 0.0379 AC XY: 2826 AN XY: 74486

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0202

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0247

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000779

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0170 Hom.: 34

Bravo AF: 0.0466

Asia WGS AF: 0.0330 AC: 113 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Mitochondrial complex IV deficiency, nuclear type 1 Benign:2

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

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.29
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

Publications

LitVar

Other links and lift over

dbSNP: rs2662956; hg19: chr17-10584164;