2-170204219-C-T

Variant names:

• chr2-170204219-C-T
• rs6738892
• NM_138995.5:c.321+3935C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138995.5(MYO3B):​c.321+3935C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,036 control chromosomes in the GnomAD database, including 22,266 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (22266 hom., cov: 33)
• Consequence: MYO3B NM_138995.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO3B	NM_138995.5	c.321+3935C>T		intron_variant	Intron 3 of 34	ENST00000408978.9	NP_620482.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO3B	ENST00000408978.9	c.321+3935C>T		intron_variant	Intron 3 of 34	1	NM_138995.5	ENSP00000386213.4

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82110 AN: 151918 Hom.: 22222 Cov.: 33

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.548

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.541 AC: 82211 AN: 152036 Hom.: 22266 Cov.: 33 AF XY: 0.544 AC XY: 40433 AN XY: 74324

African (AFR) AF: 0.571 AC: 23675 AN: 41468

American (AMR) AF: 0.614 AC: 9381 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1857 AN: 3468

East Asian (EAS) AF: 0.543 AC: 2805 AN: 5168

South Asian (SAS) AF: 0.543 AC: 2619 AN: 4820

European-Finnish (FIN) AF: 0.522 AC: 5503 AN: 10542

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34584 AN: 67980

Other (OTH) AF: 0.553 AC: 1169 AN: 2114

Alfa AF: 0.523 Hom.: 87758

Bravo AF: 0.549

Asia WGS AF: 0.570 AC: 1986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.96
DANN	Benign	0.76
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

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: rs6738892; hg19: chr2-171060729; COSMIC: COSV58706924;