NM_004589.4:c.*272T>C

Variant names:

• chr17-10680847-A-G
• rs2662956
• NM_004589.4:c.*272T>C

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.*272T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 506,918 control chromosomes in the GnomAD database, including 490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (375 hom., cov: 33)
  • Exomes 𝑓: 0.0071 (115 hom.)
• Consequence: SCO1 NM_004589.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.23
• 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=-0.92).
• BP6: Variant 17-10680847-A-G is Benign according to our data. Variant chr17-10680847-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 321788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 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.*272T>C		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.*272T>C		3_prime_UTR	Exon 6 of 6	ENSP00000255390.5	O75880
	SCO1	ENST00000901625.1		c.*272T>C		3_prime_UTR	Exon 6 of 6	ENSP00000571684.1
	SCO1	ENST00000901624.1		c.*272T>C		3_prime_UTR	Exon 6 of 6	ENSP00000571683.1

Frequencies

GnomAD3 genomes AF: 0.0388 AC: 5899 AN: 152196 Hom.: 370 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0248

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.0349

GnomAD4 exome AF: 0.00712 AC: 2525 AN: 354604 Hom.: 115 Cov.: 3 AF XY: 0.00625 AC XY: 1181 AN XY: 188918

African (AFR) AF: 0.138 AC: 1429 AN: 10366

American (AMR) AF: 0.0104 AC: 164 AN: 15710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10564

East Asian (EAS) AF: 0.0206 AC: 448 AN: 21748

South Asian (SAS) AF: 0.00226 AC: 96 AN: 42510

European-Finnish (FIN) AF: 0.0000532 AC: 1 AN: 18806

Middle Eastern (MID) AF: 0.00862 AC: 13 AN: 1508

European-Non Finnish (NFE) AF: 0.000427 AC: 91 AN: 213068

Other (OTH) AF: 0.0139 AC: 283 AN: 20324

GnomAD4 genome AF: 0.0389 AC: 5930 AN: 152314 Hom.: 375 Cov.: 33 AF XY: 0.0379 AC XY: 2826 AN XY: 74486

African (AFR) AF: 0.129 AC: 5356 AN: 41568

American (AMR) AF: 0.0202 AC: 309 AN: 15300

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

East Asian (EAS) AF: 0.0247 AC: 128 AN: 5182

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

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: 0.000779 AC: 53 AN: 68020

Other (OTH) AF: 0.0360 AC: 76 AN: 2114

Alfa AF: 0.0180 Hom.: 60

Bravo AF: 0.0466

Asia WGS AF: 0.0330 AC: 113 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)
-	-	2	not provided (2)
-	-	1	Leigh syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.29
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2662956; hg19: chr17-10584164;