2-170392430-G-C

Position:

• chr2-170392430-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138995.5(MYO3B):​c.1726G>C​(p.Glu576Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign 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: 3.83

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]

MYO3B-AS1 (HGNC:40713): (MYO3B antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21811438).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO3B	NM_138995.5	c.1726G>C	p.Glu576Gln	missense_variant	16/35	ENST00000408978.9	NP_620482.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO3B	ENST00000408978.9	c.1726G>C	p.Glu576Gln	missense_variant	16/35	1	NM_138995.5	ENSP00000386213	P1
MYO3B-AS1	ENST00000625968.2	n.54-6545C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jan 31, 2022

The c.1726G>C (p.E576Q) alteration is located in exon 16 (coding exon 16) of the MYO3B gene. This alteration results from a G to C substitution at nucleotide position 1726, causing the glutamic acid (E) at amino acid position 576 to be replaced by a glutamine (Q). 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	Benign	0.11
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.047	.;T;T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.082
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	-0.095	N;N;.
MutationTaster	Benign	0.74	D;D;D
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.20	N;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.49	T;T;T
Sift4G	Benign	0.39	.;.;T
Polyphen		0.0030	B;B;.
Vest4		0.29
MutPred		0.38		Gain of MoRF binding (P = 0.0314);Gain of MoRF binding (P = 0.0314);.;
MVP		0.88
MPC		0.079
ClinPred		0.59	D
GERP RS		5.7
Varity_R		0.27
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1558954885; hg19: chr2-171248940;