5-137870126-TAAAAAA-TAAAAAAAAA

Variant names:

• chr5-137870126-T-TAAA
• rs566265335
• NM_006790.3:c.-211-299_-211-297dupAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006790.3(MYOT):​c.-211-299_-211-297dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000046 in 86,906 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000046 (0 hom., cov: 29)
• Consequence: MYOT NM_006790.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.-211-299_-211-297dupAAA		intron	N/A	NP_006781.1	A0A0C4DFM5
	MYOT	NM_001300911.2		c.-205-299_-205-297dupAAA		intron	N/A	NP_001287840.1	B4DT68
	MYOT	NM_001135940.2		c.-281-299_-281-297dupAAA		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.-211-315_-211-314insAAA		intron	N/A	ENSP00000239926.4	A0A0C4DFM5
	MYOT	ENST00000968642.1		c.-211-315_-211-314insAAA		intron	N/A	ENSP00000638701.1
	MYOT	ENST00000515645.1	TSL:2	c.-205-315_-205-314insAAA		intron	N/A	ENSP00000426281.1	B4DT68

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 4 AN: 86906 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000793

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000251

Gnomad OTH AF: 0.000901

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

GnomAD4 genome AF: 0.0000460 AC: 4 AN: 86906 Hom.: 0 Cov.: 29 AF XY: 0.0000242 AC XY: 1 AN XY: 41272

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000793 AC: 2 AN: 25214

American (AMR) AF: 0.00 AC: 0 AN: 7784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2096

East Asian (EAS) AF: 0.00 AC: 0 AN: 3296

South Asian (SAS) AF: 0.00 AC: 0 AN: 2824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 142

European-Non Finnish (NFE) AF: 0.0000251 AC: 1 AN: 39828

Other (OTH) AF: 0.000901 AC: 1 AN: 1110

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0126737), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.45

Splicing

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

Other links and lift over

dbSNP: rs566265335; hg19: chr5-137205815;