chr2-170369295-C-T

Variant names:

• chr2-170369295-C-T
• rs754766991
• NM_138995.5:c.889C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138995.5(MYO3B):​c.889C>T​(p.His297Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: MYO3B NM_138995.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.45

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2775001).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO3B	NM_138995.5	c.889C>T	p.His297Tyr	missense_variant	Exon 9 of 35	ENST00000408978.9	NP_620482.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO3B	ENST00000408978.9	c.889C>T	p.His297Tyr	missense_variant	Exon 9 of 35	1	NM_138995.5	ENSP00000386213.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249196 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135190

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461522 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727070

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	.;T;T
Eigen	Benign	0.16
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.4	L;L;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.075
Sift	Benign	0.058	T;T;D
Sift4G	Benign	0.12	.;.;T
Polyphen		0.28	B;B;.
Vest4		0.28
MutPred		0.51		Loss of ubiquitination at K294 (P = 0.0485);Loss of ubiquitination at K294 (P = 0.0485);.;
MVP		0.71
MPC		0.087
ClinPred		0.58	D
GERP RS		5.2
Varity_R		0.12
gMVP		0.56

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

LitVar

Other links and lift over

dbSNP: rs754766991; hg19: chr2-171225805;