17-10629567-G-A

Position:

• chr17-10629567-G-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.5796+30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 1,611,162 control chromosomes in the GnomAD database, including 392,091 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (29291 hom., cov: 32)
  • Exomes 𝑓: 0.70 (362800 hom.)
• Consequence: MYH3 NM_002470.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.683

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-10629567-G-A is Benign according to our data. Variant chr17-10629567-G-A is described in ClinVar as [Benign]. Clinvar id is 258701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH3	NM_002470.4	c.5796+30C>T		intron_variant		ENST00000583535.6	NP_002461.2
MYH3	XM_011523870.4	c.5796+30C>T		intron_variant			XP_011522172.1
MYH3	XM_011523871.3	c.5796+30C>T		intron_variant			XP_011522173.1
MYH3	XM_047436127.1	c.5796+30C>T		intron_variant			XP_047292083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH3	ENST00000583535.6	c.5796+30C>T		intron_variant		5	NM_002470.4	ENSP00000464317	P1
MYH3	ENST00000577963.1	n.338+30C>T		intron_variant, non_coding_transcript_variant		2
MYH3	ENST00000579928.2	n.326+30C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89693 AN: 151584 Hom.: 29291 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.604

GnomAD3 exomes AF: 0.648 AC: 162246 AN: 250480 Hom.: 54575 AF XY: 0.655 AC XY: 88742 AN XY: 135540

Gnomad AFR exome AF: 0.299

Gnomad AMR exome AF: 0.595

Gnomad ASJ exome AF: 0.715

Gnomad EAS exome AF: 0.519

Gnomad SAS exome AF: 0.552

Gnomad FIN exome AF: 0.747

Gnomad NFE exome AF: 0.733

Gnomad OTH exome AF: 0.678

GnomAD4 exome AF: 0.699 AC: 1020484 AN: 1459464 Hom.: 362800 Cov.: 45 AF XY: 0.697 AC XY: 506337 AN XY: 726034

Gnomad4 AFR exome AF: 0.278

Gnomad4 AMR exome AF: 0.601

Gnomad4 ASJ exome AF: 0.713

Gnomad4 EAS exome AF: 0.526

Gnomad4 SAS exome AF: 0.552

Gnomad4 FIN exome AF: 0.751

Gnomad4 NFE exome AF: 0.733

Gnomad4 OTH exome AF: 0.666

GnomAD4 genome AF: 0.591 AC: 89716 AN: 151698 Hom.: 29291 Cov.: 32 AF XY: 0.589 AC XY: 43715 AN XY: 74162

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.739

Gnomad4 OTH AF: 0.606

Alfa AF: 0.630 Hom.: 4095

Bravo AF: 0.568

Asia WGS AF: 0.517 AC: 1790 AN: 3456

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Freeman-Sheldon syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Contractures, pterygia, and variable skeletal fusions syndrome 1B Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Arthrogryposis, distal, type 2B3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.5
DANN	Benign	0.88

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: rs12940161; hg19: chr17-10532884; COSMIC: COSV56865863;