chr17-10680770-G-C

Variant names:

• chr17-10680770-G-C
• rs151279533
• NM_004589.4:c.*349C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_004589.4(SCO1):​c.*349C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000586 in 368,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00072 (0 hom.)
• Consequence: SCO1 NM_004589.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:4
• Conservation: PhyloP100: -0.579
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000394 (60/152322) while in subpopulation SAS AF = 0.00663 (32/4824). AF 95% confidence interval is 0.00483. There are 0 homozygotes in GnomAd4. There are 35 alleles in the male GnomAd4 subpopulation. Median coverage is 33. 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.*349C>G		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.*349C>G		3_prime_UTR	Exon 6 of 6	ENSP00000255390.5	O75880
	SCO1	ENST00000901625.1		c.*349C>G		3_prime_UTR	Exon 6 of 6	ENSP00000571684.1
	SCO1	ENST00000901624.1		c.*349C>G		3_prime_UTR	Exon 6 of 6	ENSP00000571683.1

Frequencies

GnomAD3 genomes AF: 0.000374 AC: 57 AN: 152204 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000722 AC: 156 AN: 216152 Hom.: 0 Cov.: 0 AF XY: 0.000928 AC XY: 107 AN XY: 115324

African (AFR) AF: 0.00 AC: 0 AN: 6764

American (AMR) AF: 0.000311 AC: 3 AN: 9644

Ashkenazi Jewish (ASJ) AF: 0.000836 AC: 5 AN: 5984

East Asian (EAS) AF: 0.00 AC: 0 AN: 10702

South Asian (SAS) AF: 0.00362 AC: 119 AN: 32882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10002

Middle Eastern (MID) AF: 0.00115 AC: 1 AN: 866

European-Non Finnish (NFE) AF: 0.000172 AC: 22 AN: 127608

Other (OTH) AF: 0.000513 AC: 6 AN: 11700

GnomAD4 genome AF: 0.000394 AC: 60 AN: 152322 Hom.: 0 Cov.: 33 AF XY: 0.000470 AC XY: 35 AN XY: 74490

African (AFR) AF: 0.0000241 AC: 1 AN: 41574

American (AMR) AF: 0.000392 AC: 6 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00663 AC: 32 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000139 Hom.: 0

Bravo AF: 0.000298

Asia WGS AF: 0.00202 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	-0.88
CADD	Benign	0.56
DANN	Benign	0.59
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism

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: rs151279533; hg19: chr17-10584087;