chr17-10632032-C-G

Position:

chr17-10632032-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002470.4(MYH3):c.4957-16G>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 1,611,690 control chromosomes in the GnomAD database, including 506,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 45994 hom., cov: 34)

Exomes 𝑓: 0.79 ( 460920 hom. )

Consequence

MYH3
NM_002470.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -1.88

Variant links:

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]

MYH3 links:

LOC124903927 (HGNC:):

LOC124903927 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 17-10632032-C-G is Benign according to our data. Variant chr17-10632032-C-G is described in ClinVar as [Benign]. Clinvar id is 258691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-10632032-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH3	NM_002470.4 linkuse as main transcript	c.4957-16G>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000583535.6	NP_002461.2
LOC124903927	XR_007065620.1 linkuse as main transcript	n.221+268C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH3	ENST00000583535.6 linkuse as main transcript	c.4957-16G>C		splice_polypyrimidine_tract_variant, intron_variant		5	NM_002470.4	ENSP00000464317	P1

Frequencies

GnomAD3 genomes

AF:

0.775

AC:

117851

AN:

152050

Hom.:

45962

Cov.:

show subpopulations

Gnomad AFR

AF:

0.765

Gnomad AMI

AF:

0.792

Gnomad AMR

AF:

0.708

Gnomad ASJ

AF:

0.764

Gnomad EAS

AF:

0.538

Gnomad SAS

AF:

0.716

Gnomad FIN

AF:

0.786

Gnomad MID

AF:

0.678

Gnomad NFE

AF:

0.819

Gnomad OTH

AF:

0.747

GnomAD3 exomes

AF:

0.752

AC:

186624

AN:

248234

Hom.:

71102

AF XY:

0.756

AC XY:

101528

AN XY:

134330

show subpopulations

Gnomad AFR exome

AF:

0.773

Gnomad AMR exome

AF:

0.651

Gnomad ASJ exome

AF:

0.769

Gnomad EAS exome

AF:

0.534

Gnomad SAS exome

AF:

0.726

Gnomad FIN exome

AF:

0.798

Gnomad NFE exome

AF:

0.811

Gnomad OTH exome

AF:

0.766

GnomAD4 exome

AF:

0.793

AC:

1156688

AN:

1459522

Hom.:

460920

Cov.:

AF XY:

0.791

AC XY:

574330

AN XY:

726106

show subpopulations

Gnomad4 AFR exome

AF:

0.754

Gnomad4 AMR exome

AF:

0.660

Gnomad4 ASJ exome

AF:

0.768

Gnomad4 EAS exome

AF:

0.543

Gnomad4 SAS exome

AF:

0.723

Gnomad4 FIN exome

AF:

0.801

Gnomad4 NFE exome

AF:

0.815

Gnomad4 OTH exome

AF:

0.773

GnomAD4 genome

AF:

0.775

AC:

117943

AN:

152168

Hom.:

45994

Cov.:

AF XY:

0.768

AC XY:

57116

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.765

Gnomad4 AMR

AF:

0.708

Gnomad4 ASJ

AF:

0.764

Gnomad4 EAS

AF:

0.538

Gnomad4 SAS

AF:

0.716

Gnomad4 FIN

AF:

0.786

Gnomad4 NFE

AF:

0.818

Gnomad4 OTH

AF:

0.750

Alfa

AF:

0.770

Hom.:

5120

Bravo

AF:

0.765

Asia WGS

AF:

0.665

AC:

2316

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

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

-0.90

CADD

Benign

0.27

DANN

Benign

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over