Variant 2-170217316-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_138995.5(MYO3B):c.527-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,613,530 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0066 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00067 ( 12 hom. )

Consequence

MYO3B
NM_138995.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003186

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0470

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 2-170217316-T-C is Benign according to our data. Variant chr2-170217316-T-C is described in ClinVar as [Benign]. Clinvar id is 780855.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00655 (998/152330) while in subpopulation AFR AF= 0.0228 (949/41568). AF 95% confidence interval is 0.0216. There are 8 homozygotes in gnomad4. There are 442 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO3B	NM_138995.5 linkuse as main transcript	c.527-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000408978.9	NP_620482.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO3B	ENST00000408978.9 linkuse as main transcript	c.527-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_138995.5	ENSP00000386213	P1	Q8WXR4-1

Frequencies

GnomAD3 genomes

AF:

0.00655

AC:

997

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0229

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00180

AC:

449

AN:

249556

Hom.:

AF XY:

0.00155

AC XY:

210

AN XY:

135392

show subpopulations

Gnomad AFR exome

AF:

0.0245

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00148

GnomAD4 exome

AF:

0.000671

AC:

980

AN:

1461200

Hom.:

Cov.:

AF XY:

0.000561

AC XY:

408

AN XY:

726954

show subpopulations

Gnomad4 AFR exome

AF:

0.0238

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.00152

GnomAD4 genome

AF:

0.00655

AC:

998

AN:

152330

Hom.:

Cov.:

AF XY:

0.00593

AC XY:

442

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0228

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00369

Hom.:

Bravo

AF:

0.00810

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 15, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.3

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000032

dbscSNV1_RF

Benign

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over