rs150348272

Variant names:

• chr17-10634829-G-A
• rs150348272
• NM_002470.4:c.4356+11C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002470.4(MYH3):​c.4356+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00532 in 1,614,052 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0053 (43 hom.)
• Consequence: MYH3 NM_002470.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -4.38
• Publications: 2 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]

LOC124903927 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-10634829-G-A is Benign according to our data. Variant chr17-10634829-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00534 (7801/1461858) while in subpopulation MID AF = 0.0191 (110/5768). AF 95% confidence interval is 0.0162. There are 43 homozygotes in GnomAdExome4. There are 3962 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002470.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH3	NM_002470.4	MANE Select	c.4356+11C>T		intron	N/A	NP_002461.2	P11055

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH3	ENST00000583535.6	TSL:5 MANE Select	c.4356+11C>T		intron	N/A	ENSP00000464317.1	P11055
	MYH3	ENST00000961194.1		c.4356+11C>T		intron	N/A	ENSP00000631253.1
	MYHAS	ENST00000781814.1		n.309G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.00512 AC: 779 AN: 152074 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00471

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00708

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00810

Gnomad FIN AF: 0.000850

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.00525

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00531 AC: 1334 AN: 251422 AF XY: 0.00591

Gnomad AFR exome AF: 0.00345

Gnomad AMR exome AF: 0.00393

Gnomad ASJ exome AF: 0.0171

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00125

Gnomad NFE exome AF: 0.00583

Gnomad OTH exome AF: 0.00521

GnomAD4 exome AF: 0.00534 AC: 7801 AN: 1461858 Hom.: 43 Cov.: 32 AF XY: 0.00545 AC XY: 3962 AN XY: 727230

African (AFR) AF: 0.00490 AC: 164 AN: 33480

American (AMR) AF: 0.00407 AC: 182 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0178 AC: 466 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.00873 AC: 753 AN: 86256

European-Finnish (FIN) AF: 0.00129 AC: 69 AN: 53414

Middle Eastern (MID) AF: 0.0191 AC: 110 AN: 5768

European-Non Finnish (NFE) AF: 0.00511 AC: 5681 AN: 1111988

Other (OTH) AF: 0.00618 AC: 373 AN: 60394

GnomAD4 genome AF: 0.00513 AC: 780 AN: 152194 Hom.: 2 Cov.: 33 AF XY: 0.00493 AC XY: 367 AN XY: 74406

African (AFR) AF: 0.00474 AC: 197 AN: 41538

American (AMR) AF: 0.00707 AC: 108 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00790 AC: 38 AN: 4810

European-Finnish (FIN) AF: 0.000850 AC: 9 AN: 10594

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00526 AC: 358 AN: 68014

Other (OTH) AF: 0.00616 AC: 13 AN: 2110

Alfa AF: 0.00645 Hom.: 1

Bravo AF: 0.00585

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Distal arthrogryposis type 2B1 (1)
-	-	1	Freeman-Sheldon syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.014
DANN	Benign	0.77
PhyloP100		-4.4
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs150348272; hg19: chr17-10538146; COSMIC: COSV107313209; COSMIC: COSV107313209;