17-10674717-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.387

Publications

11 publications found

Variant links:

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]

SCO1 links:

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]

MYHAS links:

MYH3 (HGNC:7573): (myosin heavy chain 3) Myosin is a major contractile protein which converts chemical energy into mechanical energy through the hydrolysis of ATP. Myosin is a hexameric protein composed of a pair of myosin heavy chains (MYH) and two pairs of nonidentical light chains. This gene is a member of the MYH family and encodes a protein with an IQ domain and a myosin head-like domain. Mutations in this gene have been associated with two congenital contracture (arthrogryposis) syndromes, Freeman-Sheldon syndrome and Sheldon-Hall syndrome. [provided by RefSeq, Jul 2008]

MYH3 Gene-Disease associations (from GenCC):

Freeman-Sheldon syndrome
Inheritance: AD Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics
distal arthrogryposis type 2B1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
contractures, pterygia, and variable skeletal fusions syndrome 1B
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
digitotalar dysmorphism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Sheldon-hall syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive multiple pterygium syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
spondylocarpotarsal synostosis syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MYH3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
SCO1	NM_004589.4 link	c.*6402C>G	3_prime_UTR_variant	Exon 6 of 6	ENST00000255390.10	NP_004580.1	O75880
MYH3	XM_011523870.4 link	c.-68+3553C>G	intron_variant	Intron 1 of 40		XP_011522172.1	P11055
MYH3	XM_047436127.1 link	c.-3164+3553C>G	intron_variant	Intron 1 of 42		XP_047292083.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCO1	ENST00000255390.10 link	c.*6402C>G	3_prime_UTR_variant	Exon 6 of 6	1	NM_004589.4	ENSP00000255390.5	O75880
MYHAS	ENST00000579914.2 link	n.706-9218G>C	intron_variant	Intron 4 of 4	4
MYHAS	ENST00000584139.2 link	n.1042-6016G>C	intron_variant	Intron 7 of 8	3

Frequencies

GnomAD3 genomes

AF:

0.500

AC:

75901

AN:

151890

Hom.:

19694

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.425

AC XY:

AN XY:

226

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.214

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.455

AC:

101

AN:

222

Other (OTH)

AF:

0.455

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.500

AC:

76002

AN:

152008

Hom.:

19729

Cov.:

AF XY:

0.498

AC XY:

36976

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.638

AC:

26431

AN:

41438

American (AMR)

AF:

0.498

AC:

7612

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.525

AC:

1821

AN:

3468

East Asian (EAS)

AF:

0.541

AC:

2792

AN:

5162

South Asian (SAS)

AF:

0.360

AC:

1735

AN:

4822

European-Finnish (FIN)

AF:

0.439

AC:

4639

AN:

10568

Middle Eastern (MID)

AF:

0.452

AC:

131

AN:

290

European-Non Finnish (NFE)

AF:

0.432

AC:

29344

AN:

67960

Other (OTH)

AF:

0.519

AC:

1097

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1886

3773

5659

7546

9432

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.69

PhyloP100

-0.39

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over