Genetic Variant MYOT:c.-211-297delA (chr5-137870126-TA-T) – 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.-211-297delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 86,830 control chromosomes in the GnomAD database, including 173 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.048 ( 173 hom., cov: 29)

Consequence

MYOT
NM_006790.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.449

Publications

1 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 5-137870126-TA-T is Benign according to our data. Variant chr5-137870126-TA-T is described in ClinVar as Benign. ClinVar VariationId is 1259097.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 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.-211-297delA	intron	N/A	NP_006781.1	A0A0C4DFM5
MYOT	NM_001300911.2		c.-205-297delA	intron	N/A	NP_001287840.1	B4DT68
MYOT	NM_001135940.2		c.-281-297delA	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.-211-314delA	intron	N/A	ENSP00000239926.4	A0A0C4DFM5
MYOT	ENST00000968642.1		c.-211-314delA	intron	N/A	ENSP00000638701.1
MYOT	ENST00000515645.1	TSL:2	c.-205-314delA	intron	N/A	ENSP00000426281.1	B4DT68

Frequencies

GnomAD3 genomes

AF:

0.0483

AC:

4193

AN:

86836

Hom.:

173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0237

Gnomad ASJ

AF:

0.00334

Gnomad EAS

AF:

0.000911

Gnomad SAS

AF:

0.00283

Gnomad FIN

AF:

0.00736

Gnomad MID

AF:

0.0211

Gnomad NFE

AF:

0.00349

Gnomad OTH

AF:

0.0351

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

GnomAD4 genome

AF:

0.0483

AC:

4196

AN:

86830

Hom.:

173

Cov.:

AF XY:

0.0480

AC XY:

1979

AN XY:

41268

show subpopulations

African (AFR)

AF:

0.150

AC:

3783

AN:

25206

American (AMR)

AF:

0.0237

AC:

184

AN:

7780

Ashkenazi Jewish (ASJ)

AF:

0.00334

AC:

AN:

2096

East Asian (EAS)

AF:

0.000916

AC:

AN:

3276

South Asian (SAS)

AF:

0.00286

AC:

AN:

2802

European-Finnish (FIN)

AF:

0.00736

AC:

AN:

4074

Middle Eastern (MID)

AF:

0.0217

AC:

AN:

138

European-Non Finnish (NFE)

AF:

0.00349

AC:

139

AN:

39808

Other (OTH)

AF:

0.0350

AC:

AN:

1114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

164

328

493

657

821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.00

Hom.:

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

-0.45

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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