rs1554102960

Variant names:

• chr5-137875859-A-G
• rs1554102960
• NM_006790.3:c.387A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135940.2(MYOT):​c.-166A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYOT NM_001135940.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.90
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12013373).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135940.2. 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.387A>G	p.Ile129Met	missense	Exon 3 of 10	NP_006781.1	A0A0C4DFM5
	MYOT	NM_001135940.2		c.-166A>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 10	NP_001129412.1	Q9UBF9-2
	MYOT	NM_001300911.2		c.42A>G	p.Ile14Met	missense	Exon 4 of 11	NP_001287840.1	B4DT68

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOT	ENST00000239926.9	TSL:1 MANE Select	c.387A>G	p.Ile129Met	missense	Exon 3 of 10	ENSP00000239926.4	A0A0C4DFM5
	MYOT	ENST00000421631.6	TSL:2	c.-166A>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 10	ENSP00000391185.2	Q9UBF9-2
	MYOT	ENST00000968642.1		c.387A>G	p.Ile129Met	missense	Exon 3 of 10	ENSP00000638701.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Myofibrillar myopathy 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.92
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.97	T
PhyloP100		1.9
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.071
Sift	Benign	0.32	T
Sift4G	Benign	0.11	T
Vest4		0.26
MutPred		0.12		Gain of glycosylation at S134 (P = 0.1175)
MVP		0.80
MPC		0.19
ClinPred		0.20	T
GERP RS		3.2
gMVP		0.13
Mutation Taster		=96/4	polymorphism

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: rs1554102960; hg19: chr5-137211548;