17-10629564-TG-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002470.4(MYH3):c.5796+32del 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

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 -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 [Likely_benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH3	NM_002470.4	c.5796+32del		intron_variant		ENST00000583535.6
MYH3	XM_011523870.4	c.5796+32del		intron_variant
MYH3	XM_011523871.3	c.5796+32del		intron_variant
MYH3	XM_047436127.1	c.5796+32del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH3	ENST00000583535.6	c.5796+32del		intron_variant		5	NM_002470.4	P1
MYH3	ENST00000577963.1	n.338+32del		intron_variant, non_coding_transcript_variant		2
MYH3	ENST00000579928.2	n.326+32del		intron_variant, non_coding_transcript_variant		2

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

GnomAD3 exomes AF: 0.00617 AC: 1464 AN: 237438 Hom.: 38 AF XY: 0.00437 AC XY: 562 AN XY: 128690

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 SAS exome AF: 0.0000719

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

Gnomad4 AFR exome AF: 0.0733

Gnomad4 AMR exome AF: 0.00656

Gnomad4 ASJ exome AF: 0.00176

Gnomad4 EAS exome AF: 0.0000262

Gnomad4 SAS exome AF: 0.000143

Gnomad4 FIN exome AF: 0.0000192

Gnomad4 NFE exome AF: 0.000203

Gnomad4 OTH exome AF: 0.00475

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

Gnomad4 AFR AF: 0.0684

Gnomad4 AMR AF: 0.00924

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000625

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000427

Gnomad4 OTH AF: 0.0109

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

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

Apr 03, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs147333978; hg19: chr17-10532881;