17-10628938-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002470.4(MYH3):c.5797-259C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 152,312 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.013 (13 hom., cov: 32)
• Consequence: MYH3 NM_002470.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.27

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=-0.81).
• BP6: Variant 17-10628938-G-A is Benign according to our data. Variant chr17-10628938-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1197828.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0131 (1997/152312) while in subpopulation NFE AF= 0.0204 (1390/68024). AF 95% confidence interval is 0.0195. There are 13 homozygotes in gnomad4. There are 945 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1996 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH3	NM_002470.4	c.5797-259C>T		intron_variant		ENST00000583535.6
MYH3	XM_011523870.4	c.5797-259C>T		intron_variant
MYH3	XM_011523871.3	c.5797-259C>T		intron_variant
MYH3	XM_047436127.1	c.5797-259C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH3	ENST00000583535.6	c.5797-259C>T		intron_variant		5	NM_002470.4	P1
MYH3	ENST00000577963.1	n.339-259C>T		intron_variant, non_coding_transcript_variant		2
MYH3	ENST00000579928.2	n.327-259C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1996 AN: 152194 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00343

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00825

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0190

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0204

Gnomad OTH AF: 0.00910

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

GnomAD4 genome AF: 0.0131 AC: 1997 AN: 152312 Hom.: 13 Cov.: 32 AF XY: 0.0127 AC XY: 945 AN XY: 74486

Gnomad4 AFR AF: 0.00342

Gnomad4 AMR AF: 0.00824

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0193

Gnomad4 FIN AF: 0.0191

Gnomad4 NFE AF: 0.0204

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.0158 Hom.: 1

Bravo AF: 0.0112

Asia WGS AF: 0.0140 AC: 51 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.5
Dann	Benign	0.63

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: rs113330726; hg19: chr17-10532255;