2-170217377-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_138995.5(MYO3B):c.585G>A(p.Pro195=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,612,708 control chromosomes in the GnomAD database, including 250,191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (24080 hom., cov: 33)
  • Exomes 𝑓: 0.55 (226111 hom.)
• Consequence: MYO3B NM_138995.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.82

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 2-170217377-G-A is Benign according to our data. Variant chr2-170217377-G-A is described in ClinVar as [Benign]. Clinvar id is 1246117.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.82 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO3B	NM_138995.5	c.585G>A	p.Pro195=	synonymous_variant	6/35	ENST00000408978.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO3B	ENST00000408978.9	c.585G>A	p.Pro195=	synonymous_variant	6/35	1	NM_138995.5	P1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85186 AN: 151988 Hom.: 24077 Cov.: 33

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.535

GnomAD3 exomes AF: 0.548 AC: 136838 AN: 249546 Hom.: 38271 AF XY: 0.556 AC XY: 75237 AN XY: 135392

Gnomad AFR exome AF: 0.620

Gnomad AMR exome AF: 0.400

Gnomad ASJ exome AF: 0.586

Gnomad EAS exome AF: 0.584

Gnomad SAS exome AF: 0.626

Gnomad FIN exome AF: 0.592

Gnomad NFE exome AF: 0.546

Gnomad OTH exome AF: 0.547

GnomAD4 exome AF: 0.554 AC: 809645 AN: 1460602 Hom.: 226111 Cov.: 40 AF XY: 0.557 AC XY: 404595 AN XY: 726700

Gnomad4 AFR exome AF: 0.620

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.587

Gnomad4 EAS exome AF: 0.587

Gnomad4 SAS exome AF: 0.625

Gnomad4 FIN exome AF: 0.589

Gnomad4 NFE exome AF: 0.549

Gnomad4 OTH exome AF: 0.562

GnomAD4 genome AF: 0.560 AC: 85233 AN: 152106 Hom.: 24080 Cov.: 33 AF XY: 0.560 AC XY: 41668 AN XY: 74356

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.534

Alfa AF: 0.547 Hom.: 46157

Bravo AF: 0.552

Asia WGS AF: 0.606 AC: 2104 AN: 3478

EpiCase AF: 0.546

EpiControl AF: 0.545

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	0.23
Dann	Benign	0.66

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: rs2161916; hg19: chr2-171073887; COSMIC: COSV58696665;