17-10629564-TG-T

Variant names:

• chr17-10629564-TG-T
• rs147333978
• NM_002470.4:c.5796+32delC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002470.4(MYH3):​c.5796+32delC 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 1,580,332 control chromosomes in the GnomAD database, including 173 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (93 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (80 hom.)
• Consequence: MYH3 NM_002470.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.50
• 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 -16 ACMG points.

• BP6: Variant 17-10629564-TG-T is Benign according to our data. Variant chr17-10629564-TG-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0662 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002470.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH3	NM_002470.4	MANE Select	c.5796+32delC		intron	N/A	NP_002461.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH3	ENST00000583535.6	TSL:5 MANE Select	c.5796+32delC		intron	N/A	ENSP00000464317.1
	MYH3	ENST00000577963.1	TSL:2	n.338+32delC		intron	N/A
	MYHAS	ENST00000579914.2	TSL:4	n.705+15688delG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3029 AN: 151654 Hom.: 93 Cov.: 32

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00926

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000624

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000442

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00617 AC: 1464 AN: 237438 AF XY: 0.00437

Gnomad AFR exome AF: 0.0817

Gnomad AMR exome AF: 0.00627

Gnomad ASJ exome AF: 0.00136

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000364

Gnomad OTH exome AF: 0.00465

GnomAD4 exome AF: 0.00224 AC: 3202 AN: 1428566 Hom.: 80 Cov.: 30 AF XY: 0.00191 AC XY: 1355 AN XY: 710830

African (AFR) AF: 0.0733 AC: 2331 AN: 31802

American (AMR) AF: 0.00656 AC: 287 AN: 43776

Ashkenazi Jewish (ASJ) AF: 0.00176 AC: 45 AN: 25560

East Asian (EAS) AF: 0.0000262 AC: 1 AN: 38220

South Asian (SAS) AF: 0.000143 AC: 12 AN: 84090

European-Finnish (FIN) AF: 0.0000192 AC: 1 AN: 52046

Middle Eastern (MID) AF: 0.00598 AC: 25 AN: 4178

European-Non Finnish (NFE) AF: 0.000203 AC: 221 AN: 1090144

Other (OTH) AF: 0.00475 AC: 279 AN: 58750

GnomAD4 genome AF: 0.0199 AC: 3027 AN: 151766 Hom.: 93 Cov.: 32 AF XY: 0.0187 AC XY: 1388 AN XY: 74220

African (AFR) AF: 0.0684 AC: 2822 AN: 41286

American (AMR) AF: 0.00924 AC: 141 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5154

South Asian (SAS) AF: 0.000625 AC: 3 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

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

European-Non Finnish (NFE) AF: 0.000427 AC: 29 AN: 67914

Other (OTH) AF: 0.0109 AC: 23 AN: 2106

Alfa AF: 0.00103 Hom.: 0

Bravo AF: 0.0222

ClinVar

Significance: Benign/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

Apr 03, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5
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: rs147333978; hg19: chr17-10532881; COSMIC: COSV56865915;