1-24068345-C-A

Variant names:

• chr1-24068345-C-A
• rs145156576
• NM_152372.4:c.3173G>T

Variant summary

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

The NM_152372.4(MYOM3):​c.3173G>T​(p.Arg1058Leu) variant causes a missense 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1058P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MYOM3 NM_152372.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 2 publications found

Genes affected

MYOM3 (HGNC:26679): (myomesin 3) Predicted to enable actin filament binding activity and protein homodimerization activity. Predicted to be involved in muscle contraction. Predicted to be active in M band. [provided by Alliance of Genome Resources, Apr 2022]

MYOM3-AS1 (HGNC:41158): (MYOM3 antisense RNA 1)

ENSG00000225315 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152372.4. 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
	MYOM3	NM_152372.4	MANE Select	c.3173G>T	p.Arg1058Leu	missense	Exon 26 of 37	NP_689585.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOM3	ENST00000374434.4	TSL:1 MANE Select	c.3173G>T	p.Arg1058Leu	missense	Exon 26 of 37	ENSP00000363557.3	Q5VTT5-1
	MYOM3	ENST00000958997.1		c.3233G>T	p.Arg1078Leu	missense	Exon 26 of 37	ENSP00000629056.1
	MYOM3	ENST00000959000.1		c.3173G>T	p.Arg1058Leu	missense	Exon 25 of 36	ENSP00000629059.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.1
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.14
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.028	D
Polyphen		0.98	D
Vest4		0.46
MutPred		0.50		Gain of ubiquitination at K1053 (P = 0.05)
MVP		0.36
MPC		0.36
ClinPred		0.99	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.59
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.46		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.46		Position offset: -3

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

Other links and lift over

dbSNP: rs145156576; hg19: chr1-24394835;