chr17-10391659-G-A

Position:

• chr17-10391659-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MYH8	NM_002472.3	c.5664+223C>T		intron_variant		ENST00000403437.2	NP_002463.2
MYHAS	NR_125367.1	n.76+8452G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH8	ENST00000403437.2	c.5664+223C>T		intron_variant		5	NM_002472.3	ENSP00000384330	P1
	ENST00000399342.6	n.76+8452G>A		intron_variant, non_coding_transcript_variant		3
	ENST00000581304.1	n.52+8452G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.0494

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0708

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.196

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs34130444; hg19: chr17-10294976; COSMIC: COSV67971319;