17-10680809-G-A

Variant names:

• chr17-10680809-G-A
• rs2662957
• NM_004589.4:c.*310C>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.*310C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 440,046 control chromosomes in the GnomAD database, including 498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (402 hom., cov: 33)
  • Exomes 𝑓: 0.0071 (96 hom.)
• Consequence: SCO1 NM_004589.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.466
• Publications: 3 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-10680809-G-A is Benign according to our data. Variant chr17-10680809-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 321786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 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.*310C>T		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.*310C>T		3_prime_UTR	Exon 6 of 6	ENSP00000255390.5	O75880
	SCO1	ENST00000901625.1		c.*310C>T		3_prime_UTR	Exon 6 of 6	ENSP00000571684.1
	SCO1	ENST00000901624.1		c.*310C>T		3_prime_UTR	Exon 6 of 6	ENSP00000571683.1

Frequencies

GnomAD3 genomes AF: 0.0400 AC: 6081 AN: 152188 Hom.: 397 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0207

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0250

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.0392

GnomAD4 exome AF: 0.00707 AC: 2033 AN: 287740 Hom.: 96 Cov.: 0 AF XY: 0.00618 AC XY: 950 AN XY: 153670

African (AFR) AF: 0.140 AC: 1221 AN: 8730

American (AMR) AF: 0.0109 AC: 144 AN: 13218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8280

East Asian (EAS) AF: 0.0203 AC: 317 AN: 15632

South Asian (SAS) AF: 0.00224 AC: 90 AN: 40090

European-Finnish (FIN) AF: 0.0000726 AC: 1 AN: 13778

Middle Eastern (MID) AF: 0.0101 AC: 12 AN: 1186

European-Non Finnish (NFE) AF: 0.000404 AC: 69 AN: 170736

Other (OTH) AF: 0.0111 AC: 179 AN: 16090

GnomAD4 genome AF: 0.0401 AC: 6112 AN: 152306 Hom.: 402 Cov.: 33 AF XY: 0.0390 AC XY: 2907 AN XY: 74492

African (AFR) AF: 0.133 AC: 5518 AN: 41574

American (AMR) AF: 0.0206 AC: 315 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0249 AC: 129 AN: 5180

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000823 AC: 56 AN: 68012

Other (OTH) AF: 0.0402 AC: 85 AN: 2112

Alfa AF: 0.0227 Hom.: 63

Bravo AF: 0.0479

Asia WGS AF: 0.0320 AC: 112 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Mitochondrial complex IV deficiency, nuclear type 1 (2)
-	-	1	Leigh syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.74
DANN	Benign	0.61
PhyloP100		-0.47
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: rs2662957; hg19: chr17-10584126;