rs200075965

Variant names:

• chr2-170200166-T-C
• rs200075965
• NM_138995.5:c.203T>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_138995.5(MYO3B):​c.203T>C​(p.Ile68Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,612,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: MYO3B NM_138995.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02
• Publications: 0 publications found

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]

ENSG00000308085 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.409395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO3B	NM_138995.5	c.203T>C	p.Ile68Thr	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.203T>C	p.Ile68Thr	missense_variant	Exon 3 of 35	1	NM_138995.5	ENSP00000386213.4

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000685 AC: 17 AN: 248140 AF XY: 0.0000669

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000948

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1460588 Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11 AN XY: 726558

African (AFR) AF: 0.00 AC: 0 AN: 33422

American (AMR) AF: 0.0000224 AC: 1 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.000454 AC: 18 AN: 39646

South Asian (SAS) AF: 0.00 AC: 0 AN: 86024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111364

Other (OTH) AF: 0.0000166 AC: 1 AN: 60338

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152286 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74462

African (AFR) AF: 0.00 AC: 0 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000662 AC: 8

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.203T>C (p.I68T) alteration is located in exon 3 (coding exon 3) of the MYO3B gene. This alteration results from a T to C substitution at nucleotide position 203, causing the isoleucine (I) at amino acid position 68 to be replaced by a threonine (T). 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	Pathogenic	0.67
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	.;T;T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L;.
PhyloP100		8.0
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-4.5	D;D;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0010	D;D;D
Sift4G	Pathogenic	0.0010	.;.;D
Polyphen		0.97	D;D;.
Vest4		0.74
MVP		0.56
MPC		0.45
ClinPred		0.79	D
GERP RS		5.5
Varity_R		0.68
gMVP		0.60
Mutation Taster		=24/76	disease causing

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

Other links and lift over

dbSNP: rs200075965; hg19: chr2-171056676;