Variant chr10-93313149-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_013451.4(MYOF):c.5760A>G(p.Arg1920Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 1,613,844 control chromosomes in the GnomAD database, including 577,592 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 53218 hom., cov: 32)

Exomes 𝑓: 0.85 ( 524374 hom. )

Consequence

MYOF
NM_013451.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.222

Variant links:

Genes affected

MYOF (HGNC:3656): (myoferlin) Mutations in dysferlin, a protein associated with the plasma membrane, can cause muscle weakness that affects both proximal and distal muscles. The protein encoded by this gene is a type II membrane protein that is structurally similar to dysferlin. It is a member of the ferlin family and associates with both plasma and nuclear membranes. The protein contains C2 domains that play a role in calcium-mediated membrane fusion events, suggesting that it may be involved in membrane regeneration and repair. Two transcript variants encoding different isoforms have been found for this gene. Other possible variants have been detected, but their full-length nature has not been determined. [provided by RefSeq, Dec 2008]

MYOF links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 10-93313149-T-C is Benign according to our data. Variant chr10-93313149-T-C is described in ClinVar as [Benign]. Clinvar id is 1279363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOF	NM_013451.4 link	c.5760A>G	p.Arg1920Arg	synonymous_variant	51/54	ENST00000359263.9	NP_038479.1	Q9NZM1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYOF	ENST00000359263.9 link	c.5760A>G	p.Arg1920Arg	synonymous_variant	51/54	1	NM_013451.4	ENSP00000352208.4	Q9NZM1-1
MYOF	ENST00000358334.9 link	c.5721A>G	p.Arg1907Arg	synonymous_variant	50/53	1		ENSP00000351094.5	Q9NZM1-6
MYOF	ENST00000463743.5 link	n.*319A>G		non_coding_transcript_exon_variant	31/34	5		ENSP00000432708.1	H0YD14
MYOF	ENST00000463743.5 link	n.*319A>G		3_prime_UTR_variant	31/34	5		ENSP00000432708.1	H0YD14

Frequencies

GnomAD3 genomes

AF:

0.835

AC:

127020

AN:

152078

Hom.:

53186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.794

Gnomad AMI

AF:

0.705

Gnomad AMR

AF:

0.814

Gnomad ASJ

AF:

0.796

Gnomad EAS

AF:

0.906

Gnomad SAS

AF:

0.871

Gnomad FIN

AF:

0.874

Gnomad MID

AF:

0.826

Gnomad NFE

AF:

0.855

Gnomad OTH

AF:

0.835

GnomAD3 exomes

AF:

0.845

AC:

210731

AN:

249384

Hom.:

89266

AF XY:

0.849

AC XY:

114862

AN XY:

135296

show subpopulations

Gnomad AFR exome

AF:

0.794

Gnomad AMR exome

AF:

0.767

Gnomad ASJ exome

AF:

0.818

Gnomad EAS exome

AF:

0.913

Gnomad SAS exome

AF:

0.864

Gnomad FIN exome

AF:

0.878

Gnomad NFE exome

AF:

0.856

Gnomad OTH exome

AF:

0.847

GnomAD4 exome

AF:

0.847

AC:

1237388

AN:

1461648

Hom.:

524374

Cov.:

AF XY:

0.848

AC XY:

616414

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.790

Gnomad4 AMR exome

AF:

0.774

Gnomad4 ASJ exome

AF:

0.812

Gnomad4 EAS exome

AF:

0.897

Gnomad4 SAS exome

AF:

0.862

Gnomad4 FIN exome

AF:

0.878

Gnomad4 NFE exome

AF:

0.848

Gnomad4 OTH exome

AF:

0.840

GnomAD4 genome

AF:

0.835

AC:

127103

AN:

152196

Hom.:

53218

Cov.:

AF XY:

0.837

AC XY:

62316

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.794

Gnomad4 AMR

AF:

0.814

Gnomad4 ASJ

AF:

0.796

Gnomad4 EAS

AF:

0.906

Gnomad4 SAS

AF:

0.870

Gnomad4 FIN

AF:

0.874

Gnomad4 NFE

AF:

0.855

Gnomad4 OTH

AF:

0.830

Alfa

AF:

0.847

Hom.:

105548

Bravo

AF:

0.826

Asia WGS

AF:

0.828

AC:

2879

AN:

3478

EpiCase

AF:

0.853

EpiControl

AF:

0.849

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 23, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.21

Position offset: 1

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