chr17-10391659-G-A

Variant names:

• chr17-10391659-G-A
• rs34130444
• NM_002472.3:c.5664+223C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002472.3(MYH8):​c.5664+223C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,104 control chromosomes in the GnomAD database, including 2,875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2875 hom., cov: 32)
• Consequence: MYH8 NM_002472.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.07
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 17-10391659-G-A is Benign according to our data. Variant chr17-10391659-G-A is described in ClinVar as [Benign]. Clinvar id is 1178307.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH8	NM_002472.3	c.5664+223C>T		intron_variant	Intron 39 of 39	ENST00000403437.2	NP_002463.2
MYHAS	NR_125367.1	n.76+8452G>A		intron_variant	Intron 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH8	ENST00000403437.2	c.5664+223C>T		intron_variant	Intron 39 of 39	5	NM_002472.3	ENSP00000384330.2

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25489 AN: 151986 Hom.: 2876 Cov.: 32

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.168 AC: 25487 AN: 152104 Hom.: 2875 Cov.: 32 AF XY: 0.163 AC XY: 12117 AN XY: 74346

African (AFR) AF: 0.0494 AC: 2050 AN: 41518

American (AMR) AF: 0.157 AC: 2404 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 900 AN: 3466

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5182

South Asian (SAS) AF: 0.0708 AC: 340 AN: 4804

European-Finnish (FIN) AF: 0.203 AC: 2150 AN: 10582

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16897 AN: 67960

Other (OTH) AF: 0.196 AC: 413 AN: 2112

Alfa AF: 0.204 Hom.: 442

Bravo AF: 0.163

Asia WGS AF: 0.0420 AC: 148 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.18
PhyloP100		-2.1
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: rs34130444; hg19: chr17-10294976; COSMIC: COSV67971319;