2-170214741-T-A

Variant names:

• chr2-170214741-T-A
• NM_138995.5:c.439T>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_138995.5(MYO3B):​c.439T>A​(p.Leu147Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: MYO3B NM_138995.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.90

Genes affected

MYO3B (HGNC:15576): (myosin IIIB) This gene encodes one of the class III myosins. Myosins are ATPases, activated by actin, that move along actin filaments in the cell. This class of myosins are characterized by an amino-terminal kinase domain and shown to be present in photoreceptors. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.893

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO3B	NM_138995.5	c.439T>A	p.Leu147Met	missense_variant	Exon 5 of 35	ENST00000408978.9	NP_620482.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO3B	ENST00000408978.9	c.439T>A	p.Leu147Met	missense_variant	Exon 5 of 35	1	NM_138995.5	ENSP00000386213.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 15, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.439T>A (p.L147M) alteration is located in exon 5 (coding exon 5) of the MYO3B gene. This alteration results from a T to A substitution at nucleotide position 439, causing the leucine (L) at amino acid position 147 to be replaced by a methionine (M). 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	0.71
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	.;T;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.49	N
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.89	D;D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.3	M;M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Uncertain	0.55
Sift	Benign	0.056	T;D;T
Sift4G	Pathogenic	0.0	.;.;D
Polyphen		1.0	D;D;.
Vest4		0.81
MutPred		0.90		Loss of catalytic residue at L147 (P = 0.0882);Loss of catalytic residue at L147 (P = 0.0882);.;
MVP		0.65
MPC		0.43
ClinPred		0.98	D
GERP RS		3.1
Varity_R		0.67
gMVP		0.59

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: chr2-171071251;