17-10392180-C-T

Position:

• chr17-10392180-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002472.3(MYH8):​c.5569-203G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,996 control chromosomes in the GnomAD database, including 26,118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.57 (26118 hom., cov: 32)
• Consequence: MYH8 NM_002472.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.594

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-10392180-C-T is Benign according to our data. Variant chr17-10392180-C-T is described in ClinVar as [Benign]. Clinvar id is 1243083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH8	NM_002472.3	c.5569-203G>A		intron_variant		ENST00000403437.2	NP_002463.2
MYHAS	NR_125367.1	n.76+8973C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH8	ENST00000403437.2	c.5569-203G>A		intron_variant		5	NM_002472.3	ENSP00000384330	P1
	ENST00000399342.6	n.76+8973C>T		intron_variant, non_coding_transcript_variant		3
	ENST00000581304.1	n.52+8973C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87311 AN: 151878 Hom.: 26097 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.575 AC: 87380 AN: 151996 Hom.: 26118 Cov.: 32 AF XY: 0.561 AC XY: 41696 AN XY: 74270

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.603

Alfa AF: 0.572 Hom.: 31314

Bravo AF: 0.583

Asia WGS AF: 0.275 AC: 961 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.54
DANN	Benign	0.37

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: rs2270056; hg19: chr17-10295497;