Genetic Variant MYOT:c.-211-121_-211-114dupCACACACA (chr5-137870288-G-GACACACAC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_006790.3(MYOT):c.-211-121_-211-114dupCACACACA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.049 ( 215 hom., cov: 0)

Consequence

MYOT
NM_006790.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00

Publications

0 publications found

Variant links:

Genes affected

MYOT (HGNC:12399): (myotilin) This gene encodes a cystoskeletal protein which plays a significant role in the stability of thin filaments during muscle contraction. This protein binds F-actin, crosslinks actin filaments, and prevents latrunculin A-induced filament disassembly. Mutations in this gene have been associated with limb-girdle muscular dystrophy and myofibrillar myopathies. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.[provided by RefSeq, Oct 2008]

MYOT links:

PKD2L2-DT (HGNC:55557): (PKD2L2 divergent transcript)

PKD2L2-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 5-137870288-G-GACACACAC is Benign according to our data. Variant chr5-137870288-G-GACACACAC is described in ClinVar as Benign. ClinVar VariationId is 1266810.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0776 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006790.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYOT	NM_006790.3	MANE Select	c.-211-121_-211-114dupCACACACA	intron	N/A	NP_006781.1	A0A0C4DFM5
MYOT	NM_001300911.2		c.-205-121_-205-114dupCACACACA	intron	N/A	NP_001287840.1	B4DT68
MYOT	NM_001135940.2		c.-281-121_-281-114dupCACACACA	intron	N/A	NP_001129412.1	Q9UBF9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYOT	ENST00000239926.9	TSL:1 MANE Select	c.-211-153_-211-152insACACACAC	intron	N/A	ENSP00000239926.4	A0A0C4DFM5
MYOT	ENST00000968642.1		c.-211-153_-211-152insACACACAC	intron	N/A	ENSP00000638701.1
MYOT	ENST00000515645.1	TSL:2	c.-205-153_-205-152insACACACAC	intron	N/A	ENSP00000426281.1	B4DT68

Frequencies

GnomAD3 genomes

AF:

0.0489

AC:

6205

AN:

126854

Hom.:

216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0803

Gnomad AMI

AF:

0.0320

Gnomad AMR

AF:

0.0328

Gnomad ASJ

AF:

0.0253

Gnomad EAS

AF:

0.0129

Gnomad SAS

AF:

0.0228

Gnomad FIN

AF:

0.0153

Gnomad MID

AF:

0.0280

Gnomad NFE

AF:

0.0449

Gnomad OTH

AF:

0.0358

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

GnomAD4 genome

AF:

0.0489

AC:

6211

AN:

126928

Hom.:

215

Cov.:

AF XY:

0.0461

AC XY:

2774

AN XY:

60154

show subpopulations

African (AFR)

AF:

0.0802

AC:

2665

AN:

33242

American (AMR)

AF:

0.0328

AC:

399

AN:

12172

Ashkenazi Jewish (ASJ)

AF:

0.0253

AC:

AN:

3240

East Asian (EAS)

AF:

0.0130

AC:

AN:

4390

South Asian (SAS)

AF:

0.0229

AC:

AN:

3584

European-Finnish (FIN)

AF:

0.0153

AC:

103

AN:

6730

Middle Eastern (MID)

AF:

0.0299

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.0449

AC:

2727

AN:

60770

Other (OTH)

AF:

0.0360

AC:

AN:

1720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

253

507

760

1014

1267

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0205

Hom.:

147

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over