rs9897641

Variant names:

• chr17-10693063-G-A
• rs9897641
• NM_004589.4:c.365-102C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.455
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• mitochondrial complex IV deficiency, nuclear type 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 676257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004589.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCO1	NM_004589.4	MANE Select	c.365-102C>T		intron	N/A	NP_004580.1	O75880

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCO1	ENST00000255390.10	TSL:1 MANE Select	c.365-102C>T		intron	N/A	ENSP00000255390.5	O75880
	SCO1	ENST00000901625.1		c.437-102C>T		intron	N/A	ENSP00000571684.1
	SCO1	ENST00000901624.1		c.365-108C>T		intron	N/A	ENSP00000571683.1

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

African (AFR) AF: 0.0294 AC: 544 AN: 18490

American (AMR) AF: 0.0913 AC: 2357 AN: 25806

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 4607 AN: 19122

East Asian (EAS) AF: 0.000291 AC: 10 AN: 34394

South Asian (SAS) AF: 0.0288 AC: 1812 AN: 63014

European-Finnish (FIN) AF: 0.0990 AC: 4408 AN: 44528

Middle Eastern (MID) AF: 0.127 AC: 488 AN: 3842

European-Non Finnish (NFE) AF: 0.138 AC: 73576 AN: 531316

Other (OTH) AF: 0.122 AC: 4510 AN: 37066

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

African (AFR) AF: 0.0327 AC: 1352 AN: 41400

American (AMR) AF: 0.119 AC: 1818 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3466

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0260 AC: 125 AN: 4810

European-Finnish (FIN) AF: 0.0928 AC: 973 AN: 10486

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9743 AN: 67954

Other (OTH) AF: 0.127 AC: 268 AN: 2110

Alfa AF: 0.131 Hom.: 536

Bravo AF: 0.102

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.65
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9897641; hg19: chr17-10596380;