5-137870126-TAAAAAA-TAAAA

Variant names:

• chr5-137870126-TAA-T
• rs566265335
• NM_006790.3:c.-211-298_-211-297delAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_006790.3(MYOT):​c.-211-298_-211-297delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 86,870 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0028 (1 hom., cov: 29)
• Consequence: MYOT NM_006790.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 1 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0028 (243/86870) while in subpopulation AFR AF = 0.00907 (229/25254). AF 95% confidence interval is 0.00811. There are 1 homozygotes in GnomAd4. There are 108 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High AC in GnomAd4 at 243 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOT	NM_006790.3	MANE Select	c.-211-298_-211-297delAA		intron	N/A	NP_006781.1	A0A0C4DFM5
	MYOT	NM_001300911.2		c.-205-298_-205-297delAA		intron	N/A	NP_001287840.1	B4DT68
	MYOT	NM_001135940.2		c.-281-298_-281-297delAA		intron	N/A	NP_001129412.1	Q9UBF9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOT	ENST00000239926.9	TSL:1 MANE Select	c.-211-314_-211-313delAA		intron	N/A	ENSP00000239926.4	A0A0C4DFM5
	MYOT	ENST00000968642.1		c.-211-314_-211-313delAA		intron	N/A	ENSP00000638701.1
	MYOT	ENST00000515645.1	TSL:2	c.-205-314_-205-313delAA		intron	N/A	ENSP00000426281.1	B4DT68

Frequencies

GnomAD3 genomes AF: 0.00280 AC: 243 AN: 86876 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.00909

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000642

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000354

Gnomad FIN AF: 0.000492

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000100

Gnomad OTH AF: 0.00180

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

GnomAD4 genome AF: 0.00280 AC: 243 AN: 86870 Hom.: 1 Cov.: 29 AF XY: 0.00262 AC XY: 108 AN XY: 41270

African (AFR) AF: 0.00907 AC: 229 AN: 25254

American (AMR) AF: 0.000642 AC: 5 AN: 7784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2094

East Asian (EAS) AF: 0.00 AC: 0 AN: 3278

South Asian (SAS) AF: 0.000357 AC: 1 AN: 2800

European-Finnish (FIN) AF: 0.000492 AC: 2 AN: 4068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 138

European-Non Finnish (NFE) AF: 0.000100 AC: 4 AN: 39804

Other (OTH) AF: 0.00180 AC: 2 AN: 1114

Alfa AF: 0.00 Hom.: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.020
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs566265335; hg19: chr5-137205815;