NM_152372.4:c.3197T>C

Variant names:

• chr1-24068321-A-G
• rs12145360
• NM_152372.4:c.3197T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152372.4(MYOM3):​c.3197T>C​(p.Ile1066Thr) variant causes a missense change. The variant allele was found at a frequency of 0.143 in 1,613,636 control chromosomes in the GnomAD database, including 18,275 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2163 hom., cov: 31)
  • Exomes 𝑓: 0.14 (16112 hom.)
• Consequence: MYOM3 NM_152372.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.83
• Publications: 19 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016693771).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

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.3197T>C	p.Ile1066Thr	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.3197T>C	p.Ile1066Thr	missense	Exon 26 of 37	ENSP00000363557.3	Q5VTT5-1
	MYOM3	ENST00000958997.1		c.3257T>C	p.Ile1086Thr	missense	Exon 26 of 37	ENSP00000629056.1
	MYOM3	ENST00000959000.1		c.3197T>C	p.Ile1066Thr	missense	Exon 25 of 36	ENSP00000629059.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24629 AN: 151942 Hom.: 2166 Cov.: 31

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.179

GnomAD2 exomes AF: 0.163 AC: 40797 AN: 249524 AF XY: 0.168

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.135

Gnomad ASJ exome AF: 0.302

Gnomad EAS exome AF: 0.199

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.141 AC: 205575 AN: 1461576 Hom.: 16112 Cov.: 34 AF XY: 0.144 AC XY: 105004 AN XY: 727114

African (AFR) AF: 0.196 AC: 6553 AN: 33474

American (AMR) AF: 0.139 AC: 6202 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 7749 AN: 26130

East Asian (EAS) AF: 0.178 AC: 7076 AN: 39692

South Asian (SAS) AF: 0.246 AC: 21214 AN: 86238

European-Finnish (FIN) AF: 0.114 AC: 6071 AN: 53420

Middle Eastern (MID) AF: 0.260 AC: 1501 AN: 5768

European-Non Finnish (NFE) AF: 0.125 AC: 139186 AN: 1111756

Other (OTH) AF: 0.166 AC: 10023 AN: 60382

GnomAD4 genome AF: 0.162 AC: 24646 AN: 152060 Hom.: 2163 Cov.: 31 AF XY: 0.165 AC XY: 12248 AN XY: 74296

African (AFR) AF: 0.198 AC: 8219 AN: 41476

American (AMR) AF: 0.161 AC: 2455 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1012 AN: 3468

East Asian (EAS) AF: 0.205 AC: 1057 AN: 5164

South Asian (SAS) AF: 0.247 AC: 1185 AN: 4790

European-Finnish (FIN) AF: 0.118 AC: 1252 AN: 10596

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8771 AN: 67966

Other (OTH) AF: 0.177 AC: 375 AN: 2116

Alfa AF: 0.154 Hom.: 5131

Bravo AF: 0.166

TwinsUK AF: 0.125 AC: 463

ALSPAC AF: 0.128 AC: 493

ESP6500AA AF: 0.178 AC: 715

ESP6500EA AF: 0.134 AC: 1118

ExAC AF: 0.164 AC: 19763

Asia WGS AF: 0.233 AC: 810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.010
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.77	N
PhyloP100		4.8
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.063
Sift	Benign	0.28	T
Sift4G	Benign	0.10	T
Polyphen		0.016	B
Vest4		0.059
MPC		0.13
ClinPred		0.012	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.078
gMVP		0.61
Mutation Taster		=100/0	polymorphism (auto)

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: rs12145360; hg19: chr1-24394811; COSMIC: COSV58394611; COSMIC: COSV58394611;