2-170217346-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_138995.5(MYO3B):c.554G>A(p.Arg185His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00546 in 1,614,032 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0048 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (34 hom.)
• Consequence: MYO3B NM_138995.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 9.50

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00914228).
• BP6: Variant 2-170217346-G-A is Benign according to our data. Variant chr2-170217346-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651532.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO3B	NM_138995.5	c.554G>A	p.Arg185His	missense_variant	6/35	ENST00000408978.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO3B	ENST00000408978.9	c.554G>A	p.Arg185His	missense_variant	6/35	1	NM_138995.5	P1

Frequencies

GnomAD3 genomes AF: 0.00477 AC: 726 AN: 152164 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0196

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00614

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00517 AC: 1289 AN: 249562 Hom.: 10 AF XY: 0.00526 AC XY: 712 AN XY: 135398

Gnomad AFR exome AF: 0.000646

Gnomad AMR exome AF: 0.00232

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.000946

Gnomad SAS exome AF: 0.00301

Gnomad FIN exome AF: 0.0189

Gnomad NFE exome AF: 0.00576

Gnomad OTH exome AF: 0.00478

GnomAD4 exome AF: 0.00553 AC: 8085 AN: 1461750 Hom.: 34 Cov.: 30 AF XY: 0.00553 AC XY: 4020 AN XY: 727182

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.00228

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.00431

Gnomad4 SAS exome AF: 0.00301

Gnomad4 FIN exome AF: 0.0162

Gnomad4 NFE exome AF: 0.00577

Gnomad4 OTH exome AF: 0.00379

GnomAD4 genome AF: 0.00476 AC: 725 AN: 152282 Hom.: 5 Cov.: 32 AF XY: 0.00539 AC XY: 401 AN XY: 74452

Gnomad4 AFR AF: 0.000698

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0196

Gnomad4 NFE AF: 0.00613

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00504 Hom.: 1

Bravo AF: 0.00331

TwinsUK AF: 0.00647 AC: 24

ALSPAC AF: 0.00571 AC: 22

ESP6500AA AF: 0.000523 AC: 2

ESP6500EA AF: 0.00582 AC: 48

ExAC AF: 0.00489 AC: 591

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00523

EpiControl AF: 0.00450

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

MYO3B: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Uncertain	0.10
Cadd	Pathogenic	28
Dann	Benign	0.88
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D
MetaRNN	Benign	0.0091	T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.4	L;L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.5	D;D;D
REVEL	Uncertain	0.29
Sift	Benign	0.23	T;T;T
Polyphen		0.69	P;P;.
Vest4		0.63
MVP		0.87
MPC		0.16
ClinPred		0.048	T
GERP RS		6.1
Varity_R		0.39
gMVP		0.68

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: rs55911154; hg19: chr2-171073856; COSMIC: COSV100510836;