rs12940161

Variant names:

• chr17-10629567-G-A
• rs12940161
• NM_002470.4:c.5796+30C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-10629567-G-A
• chr17-10629567-G-C
• chr17-10629567-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
MYH3	NM_002470.4	c.5796+30C>T		intron_variant	Intron 40 of 40	ENST00000583535.6	NP_002461.2
MYH3	XM_011523870.4	c.5796+30C>T		intron_variant	Intron 40 of 40		XP_011522172.1
MYH3	XM_011523871.3	c.5796+30C>T		intron_variant	Intron 40 of 40		XP_011522173.1
MYH3	XM_047436127.1	c.5796+30C>T		intron_variant	Intron 42 of 42		XP_047292083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH3	ENST00000583535.6	c.5796+30C>T		intron_variant	Intron 40 of 40	5	NM_002470.4	ENSP00000464317.1

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

GnomAD2 exomes AF: 0.648 AC: 162246 AN: 250480 AF XY: 0.655

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 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

African (AFR) AF: 0.278 AC: 9281 AN: 33410

American (AMR) AF: 0.601 AC: 26891 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 18627 AN: 26134

East Asian (EAS) AF: 0.526 AC: 20861 AN: 39688

South Asian (SAS) AF: 0.552 AC: 47578 AN: 86156

European-Finnish (FIN) AF: 0.751 AC: 39965 AN: 53224

Middle Eastern (MID) AF: 0.585 AC: 2525 AN: 4314

European-Non Finnish (NFE) AF: 0.733 AC: 814620 AN: 1111602

Other (OTH) AF: 0.666 AC: 40136 AN: 60224

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

African (AFR) AF: 0.300 AC: 12321 AN: 41098

American (AMR) AF: 0.620 AC: 9483 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2467 AN: 3472

East Asian (EAS) AF: 0.522 AC: 2669 AN: 5116

South Asian (SAS) AF: 0.536 AC: 2587 AN: 4822

European-Finnish (FIN) AF: 0.740 AC: 7852 AN: 10612

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.739 AC: 50228 AN: 67984

Other (OTH) AF: 0.606 AC: 1272 AN: 2100

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Freeman-Sheldon syndrome Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Arthrogryposis, distal, type 2B3 Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.5
DANN	Benign	0.88
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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