rs73976869

chr17-10630259-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002470.4(MYH3):c.5457+29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00394 in 1,581,590 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (92 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (80 hom.)
• Consequence: MYH3 NM_002470.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.73

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-10630259-A-G is Benign according to our data. Variant chr17-10630259-A-G is described in ClinVar as [Benign]. Clinvar id is 258697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH3	NM_002470.4	c.5457+29T>C		intron_variant		ENST00000583535.6
MYH3	XM_011523870.4	c.5457+29T>C		intron_variant
MYH3	XM_011523871.3	c.5457+29T>C		intron_variant
MYH3	XM_047436127.1	c.5457+29T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH3	ENST00000583535.6	c.5457+29T>C		intron_variant		5	NM_002470.4	P1

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3007 AN: 119576 Hom.: 91 Cov.: 33

Gnomad AFR AF: 0.0722

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.00193

Gnomad EAS AF: 0.00345

Gnomad SAS AF: 0.000802

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00787

Gnomad NFE AF: 0.000565

Gnomad OTH AF: 0.0152

GnomAD3 exomes AF: 0.00588 AC: 1474 AN: 250616 Hom.: 40 AF XY: 0.00419 AC XY: 568 AN XY: 135522

Gnomad AFR exome AF: 0.0724

Gnomad AMR exome AF: 0.00567

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.00103

Gnomad SAS exome AF: 0.000359

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000334

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00220 AC: 3222 AN: 1461884 Hom.: 80 Cov.: 35 AF XY: 0.00188 AC XY: 1368 AN XY: 727242

Gnomad4 AFR exome AF: 0.0692

Gnomad4 AMR exome AF: 0.00619

Gnomad4 ASJ exome AF: 0.00119

Gnomad4 EAS exome AF: 0.000680

Gnomad4 SAS exome AF: 0.000556

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000179

Gnomad4 OTH exome AF: 0.00490

GnomAD4 genome AF: 0.0252 AC: 3013 AN: 119706 Hom.: 92 Cov.: 33 AF XY: 0.0237 AC XY: 1378 AN XY: 58096

Gnomad4 AFR AF: 0.0719

Gnomad4 AMR AF: 0.0114

Gnomad4 ASJ AF: 0.00193

Gnomad4 EAS AF: 0.00346

Gnomad4 SAS AF: 0.000802

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000565

Gnomad4 OTH AF: 0.0201

Alfa AF: 0.00987 Hom.: 6

Bravo AF: 0.0220

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 03, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.43
Dann	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs73976869; hg19: chr17-10533576;