1-24068298-C-A

Variant names:

• chr1-24068298-C-A
• NM_152372.4:c.3220G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152372.4(MYOM3):​c.3220G>T​(p.Asp1074Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYOM3 NM_152372.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.65

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.775

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOM3	NM_152372.4	c.3220G>T	p.Asp1074Tyr	missense_variant	Exon 26 of 37	ENST00000374434.4	NP_689585.3
MYOM3-AS1	XR_001737930.2	n.81+1456C>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOM3	ENST00000374434.4	c.3220G>T	p.Asp1074Tyr	missense_variant	Exon 26 of 37	1	NM_152372.4	ENSP00000363557.3
MYOM3-AS1	ENST00000429191.1	n.69+1456C>A		intron_variant	Intron 1 of 2	3
ENSG00000225315	ENST00000439239.2	n.404+4025C>A		intron_variant	Intron 3 of 3	5
MYOM3	ENST00000448831.1	n.188-11972G>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3220G>T (p.D1074Y) alteration is located in exon 26 (coding exon 25) of the MYOM3 gene. This alteration results from a G to T substitution at nucleotide position 3220, causing the aspartic acid (D) at amino acid position 1074 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.058	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-6.9	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.50		Loss of disorder (P = 0.0594);
MVP		0.23
MPC		0.50
ClinPred		0.99	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.77
gMVP		0.92

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-24394788;