rs7512

Variant names:

• chr17-10680397-G-C
• rs7512
• NM_004589.4:c.*722C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-10680397-G-C
• chr17-10680397-G-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.*722C>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 0.461 in 154,044 control chromosomes in the GnomAD database, including 16,598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16435 hom., cov: 32)
  • Exomes 𝑓: 0.37 (163 hom.)
• Consequence: SCO1 NM_004589.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.886
• Publications: 15 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=-0.86).
• BP6: Variant 17-10680397-G-C is Benign according to our data. Variant chr17-10680397-G-C is described in ClinVar as Benign. ClinVar VariationId is 321780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 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.*722C>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.*722C>G		3_prime_UTR	Exon 6 of 6	ENSP00000255390.5	O75880
	SCO1	ENST00000901625.1		c.*722C>G		3_prime_UTR	Exon 6 of 6	ENSP00000571684.1
	SCO1	ENST00000901624.1		c.*722C>G		3_prime_UTR	Exon 6 of 6	ENSP00000571683.1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70109 AN: 151834 Hom.: 16422 Cov.: 32

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.479

GnomAD4 exome AF: 0.370 AC: 774 AN: 2092 Hom.: 163 Cov.: 0 AF XY: 0.363 AC XY: 384 AN XY: 1058

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.413 AC: 171 AN: 414

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AF: 0.400 AC: 12 AN: 30

South Asian (SAS) AF: 0.244 AC: 41 AN: 168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.376 AC: 527 AN: 1400

Other (OTH) AF: 0.300 AC: 21 AN: 70

GnomAD4 genome AF: 0.462 AC: 70171 AN: 151952 Hom.: 16435 Cov.: 32 AF XY: 0.461 AC XY: 34220 AN XY: 74254

African (AFR) AF: 0.502 AC: 20822 AN: 41456

American (AMR) AF: 0.479 AC: 7311 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1832 AN: 3470

East Asian (EAS) AF: 0.542 AC: 2798 AN: 5164

South Asian (SAS) AF: 0.362 AC: 1744 AN: 4814

European-Finnish (FIN) AF: 0.440 AC: 4632 AN: 10520

Middle Eastern (MID) AF: 0.448 AC: 130 AN: 290

European-Non Finnish (NFE) AF: 0.434 AC: 29477 AN: 67940

Other (OTH) AF: 0.485 AC: 1025 AN: 2112

Alfa AF: 0.452 Hom.: 2073

Bravo AF: 0.469

Asia WGS AF: 0.482 AC: 1676 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.86
CADD	Benign	0.39
DANN	Benign	0.55
PhyloP100		-0.89
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: rs7512; hg19: chr17-10583714; COSMIC: COSV55136189; COSMIC: COSV55136189;