rs73976871

chr17-10631783-C-A

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.5160+30G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0378 in 1,614,006 control chromosomes in the GnomAD database, including 1,398 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 (140 hom., cov: 32)
  • Exomes 𝑓: 0.038 (1258 hom.)
• Consequence: MYH3 NM_002470.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.723

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]

LOC124903927 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-10631783-C-A is Benign according to our data. Variant chr17-10631783-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 258694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH3	NM_002470.4	c.5160+30G>T		intron_variant		ENST00000583535.6
LOC124903927	XR_007065620.1	n.221+19C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH3	ENST00000583535.6	c.5160+30G>T		intron_variant		5	NM_002470.4	P1

Frequencies

GnomAD3 genomes AF: 0.0391 AC: 5941 AN: 151998 Hom.: 140 Cov.: 32

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.00831

Gnomad SAS AF: 0.0696

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0349

Gnomad OTH AF: 0.0327

GnomAD3 exomes AF: 0.0331 AC: 8334 AN: 251432 Hom.: 217 AF XY: 0.0343 AC XY: 4665 AN XY: 135886

Gnomad AFR exome AF: 0.0578

Gnomad AMR exome AF: 0.0125

Gnomad ASJ exome AF: 0.0233

Gnomad EAS exome AF: 0.0103

Gnomad SAS exome AF: 0.0664

Gnomad FIN exome AF: 0.0162

Gnomad NFE exome AF: 0.0349

Gnomad OTH exome AF: 0.0305

GnomAD4 exome AF: 0.0377 AC: 55123 AN: 1461890 Hom.: 1258 Cov.: 32 AF XY: 0.0380 AC XY: 27599 AN XY: 727244

Gnomad4 AFR exome AF: 0.0651

Gnomad4 AMR exome AF: 0.0124

Gnomad4 ASJ exome AF: 0.0235

Gnomad4 EAS exome AF: 0.00945

Gnomad4 SAS exome AF: 0.0653

Gnomad4 FIN exome AF: 0.0172

Gnomad4 NFE exome AF: 0.0381

Gnomad4 OTH exome AF: 0.0385

GnomAD4 genome AF: 0.0391 AC: 5945 AN: 152116 Hom.: 140 Cov.: 32 AF XY: 0.0383 AC XY: 2848 AN XY: 74366

Gnomad4 AFR AF: 0.0612

Gnomad4 AMR AF: 0.0192

Gnomad4 ASJ AF: 0.0277

Gnomad4 EAS AF: 0.00833

Gnomad4 SAS AF: 0.0699

Gnomad4 FIN AF: 0.0136

Gnomad4 NFE AF: 0.0349

Gnomad4 OTH AF: 0.0328

Alfa AF: 0.0341 Hom.: 16

Bravo AF: 0.0391

Asia WGS AF: 0.0350 AC: 120 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 26, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.099
Dann	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs73976871; hg19: chr17-10535100;