17-10674717-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004589.4(SCO1):c.*6402C>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 0.5 in 152,314 control chromosomes in the GnomAD database, including 19,763 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.50 (19729 hom., cov: 32)
  • Exomes 𝑓: 0.43 (34 hom.)
• Consequence: SCO1 NM_004589.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387

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]

MYH3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCO1	NM_004589.4	c.*6402C>G		3_prime_UTR_variant	6/6	ENST00000255390.10
MYH3	XM_011523870.4	c.-68+3553C>G		intron_variant
MYH3	XM_047436127.1	c.-3164+3553C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCO1	ENST00000255390.10	c.*6402C>G		3_prime_UTR_variant	6/6	1	NM_004589.4	P1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75901 AN: 151890 Hom.: 19694 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.514

GnomAD4 exome AF: 0.435 AC: 133 AN: 306 Hom.: 34 Cov.: 0 AF XY: 0.425 AC XY: 96 AN XY: 226

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.300

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.455

Gnomad4 OTH exome AF: 0.455

GnomAD4 genome AF: 0.500 AC: 76002 AN: 152008 Hom.: 19729 Cov.: 32 AF XY: 0.498 AC XY: 36976 AN XY: 74284

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.519

Alfa AF: 0.310 Hom.: 699

Bravo AF: 0.515

Asia WGS AF: 0.493 AC: 1714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.47
Dann	Benign	0.69

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: rs201622; hg19: chr17-10578034; COSMIC: COSV74184674;