Genetic Variant MYOT:c.-211-123_-211-114dupCACACACACA (chr5-137870288-G-GACACACACAC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_006790.3(MYOT):c.-211-123_-211-114dupCACACACACA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.014 ( 27 hom., cov: 0)

Consequence

MYOT
NM_006790.3 intron

Scores

Not classified

Clinical Significance

Likely 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:

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ACMG classification

Classification was made for transcript

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

BP6

Variant 5-137870288-G-GACACACACAC is Benign according to our data. Variant chr5-137870288-G-GACACACACAC is described in ClinVar as Likely_benign. ClinVar VariationId is 1212515.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0136 (1722/127024) while in subpopulation NFE AF = 0.0206 (1254/60792). AF 95% confidence interval is 0.0197. There are 27 homozygotes in GnomAd4. There are 747 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 1722 AD gene.

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.-211-123_-211-114dupCACACACACA	intron	N/A	NP_006781.1	A0A0C4DFM5
MYOT	NM_001300911.2		c.-205-123_-205-114dupCACACACACA	intron	N/A	NP_001287840.1	B4DT68
MYOT	NM_001135940.2		c.-281-123_-281-114dupCACACACACA	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_-211-152insACACACACAC	intron	N/A	ENSP00000239926.4	A0A0C4DFM5
MYOT	ENST00000968642.1		c.-211-153_-211-152insACACACACAC	intron	N/A	ENSP00000638701.1
MYOT	ENST00000515645.1	TSL:2	c.-205-153_-205-152insACACACACAC	intron	N/A	ENSP00000426281.1	B4DT68

Frequencies

GnomAD3 genomes

AF:

0.0136

AC:

1722

AN:

126950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00696

Gnomad AMI

AF:

0.0123

Gnomad AMR

AF:

0.00616

Gnomad ASJ

AF:

0.00648

Gnomad EAS

AF:

0.00182

Gnomad SAS

AF:

0.0164

Gnomad FIN

AF:

0.00713

Gnomad MID

AF:

0.00699

Gnomad NFE

AF:

0.0206

Gnomad OTH

AF:

0.00823

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

GnomAD4 genome

AF:

0.0136

AC:

1722

AN:

127024

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

747

AN XY:

60196

show subpopulations

African (AFR)

AF:

0.00694

AC:

231

AN:

33304

American (AMR)

AF:

0.00616

AC:

AN:

12180

Ashkenazi Jewish (ASJ)

AF:

0.00648

AC:

AN:

3240

East Asian (EAS)

AF:

0.00182

AC:

AN:

4392

South Asian (SAS)

AF:

0.0165

AC:

AN:

3586

European-Finnish (FIN)

AF:

0.00713

AC:

AN:

6730

Middle Eastern (MID)

AF:

0.00746

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.0206

AC:

1254

AN:

60792

Other (OTH)

AF:

0.00814

AC:

AN:

1720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

151

226

302

377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0192

Hom.:

147

ClinVar

ClinVar submissions

Significance:Likely 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

(source)

Splicing

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

Publications

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5-137870288-GACACACACACACACACACACACAC-GACACACACACACACACACACACACACACACACAC

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