NM_004589.4:c.*601delA

Variant names:

• chr17-10680517-GT-G
• rs886052591
• NM_004589.4:c.*601delA

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_004589.4(SCO1):​c.*601delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 156,972 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: SCO1 NM_004589.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:3
• Conservation: PhyloP100: -0.0640
• Publications: 0 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]

MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00154 (234/151924) while in subpopulation AFR AF = 0.00386 (160/41434). AF 95% confidence interval is 0.00337. There are 1 homozygotes in GnomAd4. There are 106 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.*601delA		3_prime_UTR	Exon 6 of 6	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.*601delA		3_prime_UTR	Exon 6 of 6	ENSP00000255390.5	O75880
	SCO1	ENST00000901625.1		c.*601delA		3_prime_UTR	Exon 6 of 6	ENSP00000571684.1
	SCO1	ENST00000901624.1		c.*601delA		3_prime_UTR	Exon 6 of 6	ENSP00000571683.1

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 234 AN: 151806 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00387

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000788

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000530

Gnomad OTH AF: 0.00432

GnomAD4 exome AF: 0.000198 AC: 1 AN: 5048 Hom.: 0 Cov.: 0 AF XY: 0.000386 AC XY: 1 AN XY: 2592

African (AFR) AF: 0.0455 AC: 1 AN: 22

American (AMR) AF: 0.00 AC: 0 AN: 1212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20

East Asian (EAS) AF: 0.00 AC: 0 AN: 168

South Asian (SAS) AF: 0.00 AC: 0 AN: 572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2830

Other (OTH) AF: 0.00 AC: 0 AN: 190

GnomAD4 genome AF: 0.00154 AC: 234 AN: 151924 Hom.: 1 Cov.: 32 AF XY: 0.00143 AC XY: 106 AN XY: 74258

African (AFR) AF: 0.00386 AC: 160 AN: 41434

American (AMR) AF: 0.000787 AC: 12 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5180

South Asian (SAS) AF: 0.000417 AC: 2 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000530 AC: 36 AN: 67944

Other (OTH) AF: 0.00428 AC: 9 AN: 2104

Alfa AF: 0.000108 Hom.: 0

Bravo AF: 0.00163

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	2	-	Mitochondrial complex IV deficiency, nuclear type 1 (2)
-	1	-	Leigh syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.064

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: rs886052591; hg19: chr17-10583834;