Variant 17-10414525-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002472.3(MYH8):c.806-41T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,335,672 control chromosomes in the GnomAD database, including 142,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14488 hom., cov: 32)

Exomes 𝑓: 0.45 ( 127586 hom. )

Consequence

MYH8
NM_002472.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.02

Variant links:

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]

MYH8 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 17-10414525-A-G is Benign according to our data. Variant chr17-10414525-A-G is described in ClinVar as [Benign]. Clinvar id is 1179638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH8	NM_002472.3 linkuse as main transcript	c.806-41T>C		intron_variant		ENST00000403437.2	NP_002463.2
MYHAS	NR_125367.1 linkuse as main transcript	n.167+8287A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
MYH8	ENST00000403437.2 linkuse as main transcript	c.806-41T>C	intron_variant	5	NM_002472.3	ENSP00000384330	P1
	ENST00000399342.6 linkuse as main transcript	n.206+8248A>G	intron_variant, non_coding_transcript_variant	3
	ENST00000581304.1 linkuse as main transcript	n.143+8287A>G	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.421

AC:

63932

AN:

151860

Hom.:

14479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.480

Gnomad AMR

AF:

0.493

Gnomad ASJ

AF:

0.459

Gnomad EAS

AF:

0.867

Gnomad SAS

AF:

0.663

Gnomad FIN

AF:

0.480

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.413

Gnomad OTH

AF:

0.395

GnomAD3 exomes

AF:

0.516

AC:

114299

AN:

221648

Hom.:

31612

AF XY:

0.516

AC XY:

62116

AN XY:

120352

show subpopulations

Gnomad AFR exome

AF:

0.309

Gnomad AMR exome

AF:

0.608

Gnomad ASJ exome

AF:

0.462

Gnomad EAS exome

AF:

0.888

Gnomad SAS exome

AF:

0.654

Gnomad FIN exome

AF:

0.480

Gnomad NFE exome

AF:

0.418

Gnomad OTH exome

AF:

0.464

GnomAD4 exome

AF:

0.451

AC:

533464

AN:

1183696

Hom.:

127586

Cov.:

AF XY:

0.456

AC XY:

274175

AN XY:

600842

show subpopulations

Gnomad4 AFR exome

AF:

0.300

Gnomad4 AMR exome

AF:

0.589

Gnomad4 ASJ exome

AF:

0.463

Gnomad4 EAS exome

AF:

0.849

Gnomad4 SAS exome

AF:

0.648

Gnomad4 FIN exome

AF:

0.467

Gnomad4 NFE exome

AF:

0.411

Gnomad4 OTH exome

AF:

0.458

GnomAD4 genome

AF:

0.421

AC:

63979

AN:

151976

Hom.:

14488

Cov.:

AF XY:

0.434

AC XY:

32251

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.306

Gnomad4 AMR

AF:

0.493

Gnomad4 ASJ

AF:

0.459

Gnomad4 EAS

AF:

0.867

Gnomad4 SAS

AF:

0.662

Gnomad4 FIN

AF:

0.480

Gnomad4 NFE

AF:

0.413

Gnomad4 OTH

AF:

0.396

Alfa

AF:

0.404

Hom.:

3037

Bravo

AF:

0.413

Asia WGS

AF:

0.724

AC:

2514

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

-0.87

CADD

Benign

0.038

DANN

Benign

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over