chr17-10392304-CA-C

Variant names:

• chr17-10392304-CA-C
• rs59406509
• NM_002472.3:c.5568+237delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002472.3(MYH8):​c.5568+237delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,154 control chromosomes in the GnomAD database, including 2,330 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (2330 hom., cov: 30)
• Consequence: MYH8 NM_002472.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.614
• Publications: 0 publications found

Genes affected

MYH8 (HGNC:7578): (myosin heavy chain 8) Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is predominantly expressed in fetal skeletal muscle. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in trismus-pseudocamptodactyly syndrome. [provided by RefSeq, Sep 2009]

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 -10 ACMG points.

• BP6: Variant 17-10392304-CA-C is Benign according to our data. Variant chr17-10392304-CA-C is described in ClinVar as Benign. ClinVar VariationId is 1284218.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002472.3. 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
	MYH8	NM_002472.3	MANE Select	c.5568+237delT		intron	N/A	NP_002463.2	P13535
	MYHAS	NR_125367.1		n.76+9098delA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH8	ENST00000403437.2	TSL:5 MANE Select	c.5568+237delT		intron	N/A	ENSP00000384330.2	P13535
	MYHAS	ENST00000399342.6	TSL:3	n.76+9098delA		intron	N/A
	MYHAS	ENST00000581304.2	TSL:3	n.52+9098delA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19603 AN: 152036 Hom.: 2329 Cov.: 30

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0922

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0777

Gnomad FIN AF: 0.0196

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.0561

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.129 AC: 19629 AN: 152154 Hom.: 2330 Cov.: 30 AF XY: 0.125 AC XY: 9288 AN XY: 74390

African (AFR) AF: 0.315 AC: 13068 AN: 41468

American (AMR) AF: 0.0920 AC: 1407 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0746 AC: 259 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5178

South Asian (SAS) AF: 0.0788 AC: 380 AN: 4820

European-Finnish (FIN) AF: 0.0196 AC: 208 AN: 10604

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.0561 AC: 3817 AN: 68002

Other (OTH) AF: 0.145 AC: 306 AN: 2110

Alfa AF: 0.0205 Hom.: 13

Bravo AF: 0.143

Asia WGS AF: 0.0490 AC: 169 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.61
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: rs59406509; hg19: chr17-10295621;