NM_006790.3:c.-211-297dupA

Variant names:

• chr5-137870126-T-TA
• rs566265335
• NM_006790.3:c.-211-297dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_006790.3(MYOT):​c.-211-297dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 86,844 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.012 (10 hom., cov: 29)
• Consequence: MYOT NM_006790.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 5-137870126-T-TA is Benign according to our data. Variant chr5-137870126-T-TA is described in ClinVar as Likely_benign. ClinVar VariationId is 1196566.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0122 (1060/86844) while in subpopulation EAS AF = 0.0284 (93/3274). AF 95% confidence interval is 0.0237. There are 10 homozygotes in GnomAd4. There are 489 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1060 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.-211-297dupA		intron	N/A	NP_006781.1	A0A0C4DFM5
	MYOT	NM_001300911.2		c.-205-297dupA		intron	N/A	NP_001287840.1	B4DT68
	MYOT	NM_001135940.2		c.-281-297dupA		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_-211-314insA		intron	N/A	ENSP00000239926.4	A0A0C4DFM5
	MYOT	ENST00000968642.1		c.-211-315_-211-314insA		intron	N/A	ENSP00000638701.1
	MYOT	ENST00000515645.1	TSL:2	c.-205-315_-205-314insA		intron	N/A	ENSP00000426281.1	B4DT68

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1059 AN: 86850 Hom.: 10 Cov.: 29

Gnomad AFR AF: 0.00520

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.00239

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.00810

Gnomad MID AF: 0.0211

Gnomad NFE AF: 0.0146

Gnomad OTH AF: 0.0144

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

GnomAD4 genome AF: 0.0122 AC: 1060 AN: 86844 Hom.: 10 Cov.: 29 AF XY: 0.0119 AC XY: 489 AN XY: 41264

African (AFR) AF: 0.00519 AC: 131 AN: 25246

American (AMR) AF: 0.0175 AC: 136 AN: 7776

Ashkenazi Jewish (ASJ) AF: 0.00239 AC: 5 AN: 2094

East Asian (EAS) AF: 0.0284 AC: 93 AN: 3274

South Asian (SAS) AF: 0.0211 AC: 59 AN: 2800

European-Finnish (FIN) AF: 0.00810 AC: 33 AN: 4076

Middle Eastern (MID) AF: 0.0217 AC: 3 AN: 138

European-Non Finnish (NFE) AF: 0.0147 AC: 583 AN: 39790

Other (OTH) AF: 0.0153 AC: 17 AN: 1114

Alfa AF: 0.00246 Hom.: 3

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.45

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;