2-170200190-A-C

Variant names:

• chr2-170200190-A-C
• NM_138995.5:c.227A>C

Variant summary

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

The NM_138995.5(MYO3B):​c.227A>C​(p.Gln76Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYO3B NM_138995.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83

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]

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 rank	MANE	Protein	UniProt
MYO3B	NM_138995.5	c.227A>C	p.Gln76Pro	missense_variant	Exon 3 of 35	ENST00000408978.9	NP_620482.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO3B	ENST00000408978.9	c.227A>C	p.Gln76Pro	missense_variant	Exon 3 of 35	1	NM_138995.5	ENSP00000386213.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.026	.;T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.54	T;T;T
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.46	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.3	M;M;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.5	D;D;D
REVEL	Uncertain	0.36
Sift	Benign	0.045	D;D;D
Sift4G	Uncertain	0.011	.;.;D
Polyphen		0.71	P;P;.
Vest4		0.66
MutPred		0.58		Gain of phosphorylation at Y72 (P = 0.1487);Gain of phosphorylation at Y72 (P = 0.1487);.;
MVP		0.79
MPC		0.18
ClinPred		0.96	D
GERP RS		1.7
Varity_R		0.68
gMVP		0.74

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: chr2-171056700;