5-137870288-GACACACACACACACACACACACAC-GACACACACACACACACACAC

Variant names:

• chr5-137870288-GACAC-G
• rs35301804
• NM_006790.3:c.-211-117_-211-114delCACA

Variant summary

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

The NM_006790.3(MYOT):​c.-211-117_-211-114delCACA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0010 (0 hom., cov: 0)
• Consequence: MYOT NM_006790.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475
• Publications: 0 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 = 0.00102 (129/127074) while in subpopulation AFR AF = 0.00243 (81/33304). AF 95% confidence interval is 0.002. There are 0 homozygotes in GnomAd4. There are 68 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 129 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.-211-117_-211-114delCACA		intron	N/A	NP_006781.1	A0A0C4DFM5
	MYOT	NM_001300911.2		c.-205-117_-205-114delCACA		intron	N/A	NP_001287840.1	B4DT68
	MYOT	NM_001135940.2		c.-281-117_-281-114delCACA		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.-211-152_-211-149delACAC		intron	N/A	ENSP00000239926.4	A0A0C4DFM5
	MYOT	ENST00000968642.1		c.-211-152_-211-149delACAC		intron	N/A	ENSP00000638701.1
	MYOT	ENST00000515645.1	TSL:2	c.-205-152_-205-149delACAC		intron	N/A	ENSP00000426281.1	B4DT68

Frequencies

GnomAD3 genomes AF: 0.000992 AC: 126 AN: 127000 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00238

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00123

Gnomad ASJ AF: 0.000926

Gnomad EAS AF: 0.00113

Gnomad SAS AF: 0.000832

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000329

Gnomad OTH AF: 0.000588

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

GnomAD4 genome AF: 0.00102 AC: 129 AN: 127074 Hom.: 0 Cov.: 0 AF XY: 0.00113 AC XY: 68 AN XY: 60216

African (AFR) AF: 0.00243 AC: 81 AN: 33304

American (AMR) AF: 0.00123 AC: 15 AN: 12180

Ashkenazi Jewish (ASJ) AF: 0.000926 AC: 3 AN: 3238

East Asian (EAS) AF: 0.00137 AC: 6 AN: 4392

South Asian (SAS) AF: 0.000836 AC: 3 AN: 3590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.000329 AC: 20 AN: 60836

Other (OTH) AF: 0.000581 AC: 1 AN: 1720

Alfa AF: 0.00 Hom.: 147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.47

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: rs35301804; hg19: chr5-137205977;