17-10629568-G-C

Variant names:

• chr17-10629568-G-C
• rs570950857
• NM_002470.4:c.5796+29C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002470.4(MYH3):​c.5796+29C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,611,944 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (93 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (79 hom.)
• Consequence: MYH3 NM_002470.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.88
• Publications: 0 publications found

Genes affected

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]

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=-0.82).
• BP6: Variant 17-10629568-G-C is Benign according to our data. Variant chr17-10629568-G-C is described in CliVar as Likely_benign. Clinvar id is 258700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-10629568-G-C is described in CliVar as Likely_benign. Clinvar id is 258700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-10629568-G-C is described in CliVar as Likely_benign. Clinvar id is 258700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH3	NM_002470.4	c.5796+29C>G		intron_variant	Intron 40 of 40	ENST00000583535.6	NP_002461.2
MYH3	XM_011523870.4	c.5796+29C>G		intron_variant	Intron 40 of 40		XP_011522172.1
MYH3	XM_011523871.3	c.5796+29C>G		intron_variant	Intron 40 of 40		XP_011522173.1
MYH3	XM_047436127.1	c.5796+29C>G		intron_variant	Intron 42 of 42		XP_047292083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH3	ENST00000583535.6	c.5796+29C>G		intron_variant	Intron 40 of 40	5	NM_002470.4	ENSP00000464317.1

Frequencies

GnomAD3 genomes AF: 0.0198 AC: 3012 AN: 152128 Hom.: 93 Cov.: 33

Gnomad AFR AF: 0.0682

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00851

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00579 AC: 1453 AN: 250874 AF XY: 0.00408

Gnomad AFR exome AF: 0.0729

Gnomad AMR exome AF: 0.00573

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000335

Gnomad OTH exome AF: 0.00441

GnomAD4 exome AF: 0.00215 AC: 3145 AN: 1459698 Hom.: 79 Cov.: 37 AF XY: 0.00183 AC XY: 1329 AN XY: 726134

African (AFR) AF: 0.0697 AC: 2329 AN: 33420

American (AMR) AF: 0.00624 AC: 279 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00119 AC: 31 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53248

Middle Eastern (MID) AF: 0.00576 AC: 25 AN: 4340

European-Non Finnish (NFE) AF: 0.000175 AC: 195 AN: 1111762

Other (OTH) AF: 0.00460 AC: 277 AN: 60228

GnomAD4 genome AF: 0.0198 AC: 3011 AN: 152246 Hom.: 93 Cov.: 33 AF XY: 0.0185 AC XY: 1378 AN XY: 74450

African (AFR) AF: 0.0680 AC: 2822 AN: 41524

American (AMR) AF: 0.00850 AC: 130 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68018

Other (OTH) AF: 0.0109 AC: 23 AN: 2112

Alfa AF: 0.000928 Hom.: 0

Bravo AF: 0.0221

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.16
DANN	Benign	0.78
PhyloP100		-1.9
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: rs570950857; hg19: chr17-10532885;