rs116773838

Variant names:

• chr5-137882069-G-A
• rs116773838
• NM_006790.3:c.780G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-137882069-G-A
• chr5-137882069-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006790.3(MYOT):​c.780G>A​(p.Ser260Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,614,132 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (51 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (61 hom.)
• Consequence: MYOT NM_006790.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -1.63
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 5-137882069-G-A is Benign according to our data. Variant chr5-137882069-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 129684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.63 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0519 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.780G>A	p.Ser260Ser	synonymous	Exon 6 of 10	NP_006781.1	A0A0C4DFM5
	MYOT	NM_001300911.2		c.435G>A	p.Ser145Ser	synonymous	Exon 7 of 11	NP_001287840.1	B4DT68
	MYOT	NM_001135940.2		c.228G>A	p.Ser76Ser	synonymous	Exon 6 of 10	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.780G>A	p.Ser260Ser	synonymous	Exon 6 of 10	ENSP00000239926.4	A0A0C4DFM5
	MYOT	ENST00000968642.1		c.777G>A	p.Ser259Ser	synonymous	Exon 6 of 10	ENSP00000638701.1
	MYOT	ENST00000515645.1	TSL:2	c.435G>A	p.Ser145Ser	synonymous	Exon 7 of 11	ENSP00000426281.1	B4DT68

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2251 AN: 152172 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00364 AC: 916 AN: 251486 AF XY: 0.00263

Gnomad AFR exome AF: 0.0517

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000105

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00154 AC: 2254 AN: 1461842 Hom.: 61 Cov.: 32 AF XY: 0.00136 AC XY: 987 AN XY: 727226

African (AFR) AF: 0.0539 AC: 1806 AN: 33476

American (AMR) AF: 0.00181 AC: 81 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000857 AC: 34 AN: 39690

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00399 AC: 23 AN: 5768

European-Non Finnish (NFE) AF: 0.000128 AC: 142 AN: 1111990

Other (OTH) AF: 0.00265 AC: 160 AN: 60390

GnomAD4 genome AF: 0.0148 AC: 2260 AN: 152290 Hom.: 51 Cov.: 32 AF XY: 0.0144 AC XY: 1069 AN XY: 74470

African (AFR) AF: 0.0518 AC: 2153 AN: 41546

American (AMR) AF: 0.00458 AC: 70 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68036

Other (OTH) AF: 0.0104 AC: 22 AN: 2110

Alfa AF: 0.00699 Hom.: 12

Bravo AF: 0.0163

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	4	Myofibrillar myopathy 3 (4)
-	-	1	Limb-Girdle Muscular Dystrophy, Dominant (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.8
DANN	Benign	0.81
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs116773838; hg19: chr5-137217758;