5-137870288-GACACACACACACACACACACACAC-GACACACACACACACACACACACACAC

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006790.3(MYOT):​c.-211-115_-211-114dupCA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.48 (15145 hom., cov: 0)
• Consequence: MYOT NM_006790.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 5-137870288-G-GAC is Benign according to our data. Variant chr5-137870288-G-GAC is described in ClinVar as Benign. ClinVar VariationId is 1261559.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

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_-211-114dupCA		intron	N/A	NP_006781.1	A0A0C4DFM5
	MYOT	NM_001300911.2		c.-205-115_-205-114dupCA		intron	N/A	NP_001287840.1	B4DT68
	MYOT	NM_001135940.2		c.-281-115_-281-114dupCA		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.-211-153_-211-152insAC		intron	N/A	ENSP00000239926.4	A0A0C4DFM5
	MYOT	ENST00000968642.1		c.-211-153_-211-152insAC		intron	N/A	ENSP00000638701.1
	MYOT	ENST00000515645.1	TSL:2	c.-205-153_-205-152insAC		intron	N/A	ENSP00000426281.1	B4DT68

Frequencies

GnomAD3 genomes AF: 0.482 AC: 61074 AN: 126684 Hom.: 15138 Cov.: 0

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.539

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.482 AC: 61095 AN: 126756 Hom.: 15145 Cov.: 0 AF XY: 0.482 AC XY: 28928 AN XY: 60044

African (AFR) AF: 0.314 AC: 10440 AN: 33226

American (AMR) AF: 0.517 AC: 6277 AN: 12136

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 1893 AN: 3230

East Asian (EAS) AF: 0.533 AC: 2338 AN: 4384

South Asian (SAS) AF: 0.456 AC: 1635 AN: 3584

European-Finnish (FIN) AF: 0.565 AC: 3791 AN: 6712

Middle Eastern (MID) AF: 0.530 AC: 140 AN: 264

European-Non Finnish (NFE) AF: 0.547 AC: 33201 AN: 60694

Other (OTH) AF: 0.515 AC: 884 AN: 1716

Alfa AF: 0.598 Hom.: 147

ClinVar

ClinVar submissions

Significance: 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		0.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs35301804; hg19: chr5-137205977; COSMIC: COSV53513599;