5-137870288-GACACACACACACACACACACACAC-GACACACACACACACACAC

Variant names:

• chr5-137870288-GACACAC-G
• rs35301804
• NM_006790.3:c.-211-119_-211-114delCACACA

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_006790.3(MYOT):​c.-211-119_-211-114delCACACA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (115 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: MYOT NM_006790.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 5-137870288-GACACAC-G is Benign according to our data. Variant chr5-137870288-GACACAC-G is described in ClinVar as Benign. ClinVar VariationId is 1295552.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-211-119_-211-114delCACACA		intron	N/A	NP_006781.1	A0A0C4DFM5
	MYOT	NM_001300911.2		c.-205-119_-205-114delCACACA		intron	N/A	NP_001287840.1	B4DT68
	MYOT	NM_001135940.2		c.-281-119_-281-114delCACACA		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_-211-147delACACAC		intron	N/A	ENSP00000239926.4	A0A0C4DFM5
	MYOT	ENST00000968642.1		c.-211-152_-211-147delACACAC		intron	N/A	ENSP00000638701.1
	MYOT	ENST00000515645.1	TSL:2	c.-205-152_-205-147delACACAC		intron	N/A	ENSP00000426281.1	B4DT68

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3079 AN: 127002 Hom.: 115 Cov.: 0

Gnomad AFR AF: 0.0865

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0127

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000277

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000345

Gnomad OTH AF: 0.0176

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0243 AC: 3083 AN: 127074 Hom.: 115 Cov.: 0 AF XY: 0.0241 AC XY: 1451 AN XY: 60224

African (AFR) AF: 0.0865 AC: 2879 AN: 33300

American (AMR) AF: 0.0126 AC: 153 AN: 12182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3238

East Asian (EAS) AF: 0.00 AC: 0 AN: 4392

South Asian (SAS) AF: 0.00 AC: 0 AN: 3590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6736

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

European-Non Finnish (NFE) AF: 0.000345 AC: 21 AN: 60836

Other (OTH) AF: 0.0174 AC: 30 AN: 1720

Alfa AF: 0.00 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		0.47
Mutation Taster		=100/0	polymorphism

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;