chr1-24068321-A-G

Position:

• chr1-24068321-A-G

Variant summary

Our verdict is Benign. Variant got -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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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)

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOM3	NM_152372.4	c.3197T>C	p.Ile1066Thr	missense_variant	26/37	ENST00000374434.4	NP_689585.3
MYOM3-AS1	XR_001737930.2	n.81+1479A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOM3	ENST00000374434.4	c.3197T>C	p.Ile1066Thr	missense_variant	26/37	1	NM_152372.4	ENSP00000363557	P1
MYOM3-AS1	ENST00000429191.1	n.69+1479A>G		intron_variant, non_coding_transcript_variant		3
	ENST00000439239.2	n.404+4048A>G		intron_variant, non_coding_transcript_variant		5
MYOM3	ENST00000448831.1	n.188-11995T>C		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes AF: 0.163 AC: 40797 AN: 249524 Hom.: 3750 AF XY: 0.168 AC XY: 22805 AN XY: 135380

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 SAS exome AF: 0.245

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

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.297

Gnomad4 EAS exome AF: 0.178

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.166

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

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.177

Alfa AF: 0.151 Hom.: 3236

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 v4.3

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
MutationTaster	Benign	0.050	P;P;P
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

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

Publications

LitVar

Other links and lift over

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