1-24064087-C-A

Position:

• chr1-24064087-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152372.4(MYOM3):​c.3607G>T​(p.Asp1203Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 3.14

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]

ENSG00000225315 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOM3	NM_152372.4	c.3607G>T	p.Asp1203Tyr	missense_variant	30/37	ENST00000374434.4	NP_689585.3
LOC107984931	XR_001737929.1	n.316C>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOM3	ENST00000374434.4	c.3607G>T	p.Asp1203Tyr	missense_variant	30/37	1	NM_152372.4	ENSP00000363557.3
MYOM3	ENST00000338909.9	c.286G>T	p.Asp96Tyr	missense_variant	3/10	2		ENSP00000342689.5
ENSG00000225315	ENST00000439239.2	n.218C>A		non_coding_transcript_exon_variant	3/4	5
MYOM3	ENST00000448831.1	n.188-7761G>T		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.3607G>T (p.D1203Y) alteration is located in exon 30 (coding exon 29) of the MYOM3 gene. This alteration results from a G to T substitution at nucleotide position 3607, causing the aspartic acid (D) at amino acid position 1203 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	0.59
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	.;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Uncertain	-0.0065	T
MutationAssessor	Uncertain	2.8	.;M
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.2	D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.57	P;D
Vest4		0.68
MutPred		0.41		.;Loss of disorder (P = 0.0321);
MVP		0.71
MPC		0.51
ClinPred		0.99	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-24390577;