17-10680849-A-T

Variant names:

• chr17-10680849-A-T
• rs76465133
• NM_004589.4:c.*270T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004589.4(SCO1):​c.*270T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00381 in 510,036 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (35 hom.)
• Consequence: SCO1 NM_004589.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.280
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-10680849-A-T is Benign according to our data. Variant chr17-10680849-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 890068.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00175 (267/152352) while in subpopulation EAS AF = 0.0245 (127/5180). AF 95% confidence interval is 0.0211. There are 6 homozygotes in GnomAd4. There are 150 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

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.*270T>A		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.*270T>A		3_prime_UTR	Exon 6 of 6	ENSP00000255390.5	O75880
	SCO1	ENST00000901625.1		c.*270T>A		3_prime_UTR	Exon 6 of 6	ENSP00000571684.1
	SCO1	ENST00000901624.1		c.*270T>A		3_prime_UTR	Exon 6 of 6	ENSP00000571683.1

Frequencies

GnomAD3 genomes AF: 0.00173 AC: 264 AN: 152234 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0247

Gnomad SAS AF: 0.0161

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00469 AC: 1676 AN: 357684 Hom.: 35 Cov.: 3 AF XY: 0.00572 AC XY: 1091 AN XY: 190720

African (AFR) AF: 0.000192 AC: 2 AN: 10428

American (AMR) AF: 0.00 AC: 0 AN: 15918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10624

East Asian (EAS) AF: 0.0275 AC: 604 AN: 21924

South Asian (SAS) AF: 0.0218 AC: 933 AN: 42812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19002

Middle Eastern (MID) AF: 0.00196 AC: 3 AN: 1532

European-Non Finnish (NFE) AF: 0.000247 AC: 53 AN: 214948

Other (OTH) AF: 0.00395 AC: 81 AN: 20496

GnomAD4 genome AF: 0.00175 AC: 267 AN: 152352 Hom.: 6 Cov.: 32 AF XY: 0.00201 AC XY: 150 AN XY: 74496

African (AFR) AF: 0.000168 AC: 7 AN: 41588

American (AMR) AF: 0.000980 AC: 15 AN: 15302

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

East Asian (EAS) AF: 0.0245 AC: 127 AN: 5180

South Asian (SAS) AF: 0.0159 AC: 77 AN: 4828

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68032

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

Alfa AF: 0.000265 Hom.: 0

Bravo AF: 0.00148

Asia WGS AF: 0.0280 AC: 98 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Leigh syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.44
DANN	Benign	0.54
PhyloP100		-0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs76465133; hg19: chr17-10584166;