rs9897641

chr17-10693063-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004589.4(SCO1):c.365-102C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 929,464 control chromosomes in the GnomAD database, including 7,593 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1070 hom., cov: 33)
  • Exomes 𝑓: 0.12 (6523 hom.)
• Consequence: SCO1 NM_004589.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.455

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-10693063-G-A is Benign according to our data. Variant chr17-10693063-G-A is described in ClinVar as [Benign]. Clinvar id is 676257.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCO1	NM_004589.4	c.365-102C>T		intron_variant		ENST00000255390.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCO1	ENST00000255390.10	c.365-102C>T		intron_variant		1	NM_004589.4	P1
SCO1	ENST00000577427.1	c.365-102C>T		intron_variant		3
SCO1	ENST00000577335.2	c.*92-102C>T		intron_variant, NMD_transcript_variant		3
SCO1	ENST00000582053.1	n.528-102C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15382 AN: 151768 Hom.: 1072 Cov.: 33

Gnomad AFR AF: 0.0328

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0260

Gnomad FIN AF: 0.0928

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.119 AC: 92312 AN: 777578 Hom.: 6523 AF XY: 0.116 AC XY: 46827 AN XY: 402654

Gnomad4 AFR exome AF: 0.0294

Gnomad4 AMR exome AF: 0.0913

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.000291

Gnomad4 SAS exome AF: 0.0288

Gnomad4 FIN exome AF: 0.0990

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.122

GnomAD4 genome AF: 0.101 AC: 15373 AN: 151886 Hom.: 1070 Cov.: 33 AF XY: 0.0980 AC XY: 7270 AN XY: 74188

Gnomad4 AFR AF: 0.0327

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0260

Gnomad4 FIN AF: 0.0928

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.127

Alfa AF: 0.130 Hom.: 307

Bravo AF: 0.102

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.3
Dann	Benign	0.65

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: rs9897641; hg19: chr17-10596380;