1-24068345-C-G

Variant names:

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

Variant summary

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

The NM_152372.4(MYOM3):​c.3173G>C​(p.Arg1058Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000953 in 1,614,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1058G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00070 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00098 (0 hom.)
• Consequence: MYOM3 NM_152372.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 0 ACMG points.

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>C	p.Arg1058Pro	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>C	p.Arg1058Pro	missense	Exon 26 of 37	ENSP00000363557.3	Q5VTT5-1
	MYOM3	ENST00000958997.1		c.3233G>C	p.Arg1078Pro	missense	Exon 26 of 37	ENSP00000629056.1
	MYOM3	ENST00000959000.1		c.3173G>C	p.Arg1058Pro	missense	Exon 25 of 36	ENSP00000629059.1

Frequencies

GnomAD3 genomes AF: 0.000703 AC: 107 AN: 152152 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00115

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000685 AC: 171 AN: 249536 AF XY: 0.000717

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.000435

Gnomad ASJ exome AF: 0.00298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000371

Gnomad NFE exome AF: 0.000980

Gnomad OTH exome AF: 0.000661

GnomAD4 exome AF: 0.000979 AC: 1431 AN: 1461860 Hom.: 0 Cov.: 33 AF XY: 0.000952 AC XY: 692 AN XY: 727230

African (AFR) AF: 0.000179 AC: 6 AN: 33478

American (AMR) AF: 0.000403 AC: 18 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00337 AC: 88 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.000393 AC: 21 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00110 AC: 1224 AN: 1111988

Other (OTH) AF: 0.00118 AC: 71 AN: 60394

GnomAD4 genome AF: 0.000703 AC: 107 AN: 152270 Hom.: 0 Cov.: 31 AF XY: 0.000672 AC XY: 50 AN XY: 74460

African (AFR) AF: 0.000120 AC: 5 AN: 41548

American (AMR) AF: 0.000196 AC: 3 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.000941 AC: 10 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00115 AC: 78 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00104 Hom.: 0

Bravo AF: 0.000718

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00134 AC: 11

ExAC AF: 0.000604 AC: 73

EpiCase AF: 0.000927

EpiControl AF: 0.000711

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.0093	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.1
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.14
Sift	Benign	0.049	D
Sift4G	Benign	0.098	T
Polyphen		0.084	B
Vest4		0.23
MVP		0.39
MPC		0.13
ClinPred		0.031	T
GERP RS		3.8
Varity_R		0.61
gMVP		0.80
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.32		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;