5-137870288-GACACACACACACACACACACACAC-GACACACACACACACACACACAC

Variant names:

• chr5-137870288-GAC-G
• rs35301804
• NM_006790.3:c.-211-115_-211-114delCA

Variant summary

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

The NM_006790.3(MYOT):​c.-211-115_-211-114delCA 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 0.011 (11 hom., cov: 0)
• Consequence: MYOT NM_006790.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• 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 eas. GnomAd4 allele frequency = 0.0113 (1431/127052) while in subpopulation EAS AF = 0.0196 (86/4392). AF 95% confidence interval is 0.0162. There are 11 homozygotes in GnomAd4. There are 645 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1431 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.-211-115_-211-114delCA		intron	N/A	NP_006781.1	A0A0C4DFM5
	MYOT	NM_001300911.2		c.-205-115_-205-114delCA		intron	N/A	NP_001287840.1	B4DT68
	MYOT	NM_001135940.2		c.-281-115_-281-114delCA		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_-211-151delAC		intron	N/A	ENSP00000239926.4	A0A0C4DFM5
	MYOT	ENST00000968642.1		c.-211-152_-211-151delAC		intron	N/A	ENSP00000638701.1
	MYOT	ENST00000515645.1	TSL:2	c.-205-152_-205-151delAC		intron	N/A	ENSP00000426281.1	B4DT68

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1423 AN: 126978 Hom.: 11 Cov.: 0

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.0346

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00618

Gnomad EAS AF: 0.0195

Gnomad SAS AF: 0.0119

Gnomad FIN AF: 0.00520

Gnomad MID AF: 0.0140

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.0153

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

GnomAD4 genome AF: 0.0113 AC: 1431 AN: 127052 Hom.: 11 Cov.: 0 AF XY: 0.0107 AC XY: 645 AN XY: 60210

African (AFR) AF: 0.0106 AC: 353 AN: 33304

American (AMR) AF: 0.0101 AC: 123 AN: 12180

Ashkenazi Jewish (ASJ) AF: 0.00618 AC: 20 AN: 3238

East Asian (EAS) AF: 0.0196 AC: 86 AN: 4392

South Asian (SAS) AF: 0.0120 AC: 43 AN: 3588

European-Finnish (FIN) AF: 0.00520 AC: 35 AN: 6726

Middle Eastern (MID) AF: 0.0149 AC: 4 AN: 268

European-Non Finnish (NFE) AF: 0.0117 AC: 713 AN: 60826

Other (OTH) AF: 0.0151 AC: 26 AN: 1720

Alfa AF: 0.00530 Hom.: 147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0

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;