17-10629351-A-C

Position:

• chr17-10629351-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002470.4(MYH3):​c.5796+246T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0518 in 152,138 control chromosomes in the GnomAD database, including 461 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.052 (461 hom., cov: 32)
• Consequence: MYH3 NM_002470.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.175

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 17-10629351-A-C is Benign according to our data. Variant chr17-10629351-A-C is described in ClinVar as [Benign]. Clinvar id is 1295687.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH3	NM_002470.4	c.5796+246T>G		intron_variant		ENST00000583535.6	NP_002461.2
MYH3	XM_011523870.4	c.5796+246T>G		intron_variant			XP_011522172.1
MYH3	XM_011523871.3	c.5796+246T>G		intron_variant			XP_011522173.1
MYH3	XM_047436127.1	c.5796+246T>G		intron_variant			XP_047292083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH3	ENST00000583535.6	c.5796+246T>G		intron_variant		5	NM_002470.4	ENSP00000464317	P1
MYH3	ENST00000577963.1	n.338+246T>G		intron_variant, non_coding_transcript_variant		2
MYH3	ENST00000579928.2	n.326+246T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0519 AC: 7888 AN: 152022 Hom.: 462 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0213

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0766

Gnomad FIN AF: 0.0123

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0359

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0518 AC: 7886 AN: 152138 Hom.: 461 Cov.: 32 AF XY: 0.0510 AC XY: 3791 AN XY: 74380

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0213

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0769

Gnomad4 FIN AF: 0.0123

Gnomad4 NFE AF: 0.0175

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0363 Hom.: 29

Bravo AF: 0.0553

Asia WGS AF: 0.0430 AC: 150 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.0
DANN	Benign	0.41

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: rs112009801; hg19: chr17-10532668;