rs751530763

Variant names:

• chr5-137886001-CT-C
• rs751530763
• NM_006790.3:c.1025-41delT

Your query was ambiguous. Multiple possible variants found:

• chr5-137886001-CT-C
• chr5-137886001-CT-CTT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BS2

The NM_006790.3(MYOT):​c.1025-41delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,166,366 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: MYOT NM_006790.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.642
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 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.1025-41delT		intron	N/A	NP_006781.1	A0A0C4DFM5
	MYOT	NM_001300911.2		c.680-41delT		intron	N/A	NP_001287840.1	B4DT68
	MYOT	NM_001135940.2		c.473-41delT		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.1025-46delT		intron	N/A	ENSP00000239926.4	A0A0C4DFM5
	MYOT	ENST00000968642.1		c.1022-46delT		intron	N/A	ENSP00000638701.1
	MYOT	ENST00000968644.1		c.887-46delT		intron	N/A	ENSP00000638703.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000429 AC: 5 AN: 1166366 Hom.: 0 Cov.: 16 AF XY: 0.00000170 AC XY: 1 AN XY: 589530

African (AFR) AF: 0.00 AC: 0 AN: 25230

American (AMR) AF: 0.00 AC: 0 AN: 36760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22996

East Asian (EAS) AF: 0.00 AC: 0 AN: 34634

South Asian (SAS) AF: 0.00 AC: 0 AN: 70314

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3640

European-Non Finnish (NFE) AF: 0.00000571 AC: 5 AN: 874940

Other (OTH) AF: 0.00 AC: 0 AN: 49476

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs751530763; hg19: chr5-137221690;