Variant 17-29074834-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_078471.4(MYO18A):c.6101G>A(p.Arg2034Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,613,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

MYO18A
NM_078471.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0910

Variant links:

Genes affected

MYO18A (HGNC:31104): (myosin XVIIIA) The protein encoded by this gene can bind GOLPH3, linking the Golgi to the cytoskeleton and influencing Golgi membrane trafficking. The encoded protein is also part of a complex that assembles lamellar actomyosin bundles and may be required for cell migration. [provided by RefSeq, Oct 2016]

MYO18A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant where missense usually causes diseases, MYO18A

BP4

Computational evidence support a benign effect (MetaRNN=0.08167735).

BS2

High AC in GnomAd at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO18A	NM_078471.4 linkuse as main transcript	c.6101G>A	p.Arg2034Gln	missense_variant	42/42	ENST00000527372.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO18A	ENST00000527372.7 linkuse as main transcript	c.6101G>A	p.Arg2034Gln	missense_variant	42/42	1	NM_078471.4	A1	Q92614-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000129

AC:

AN:

247982

Hom.:

AF XY:

0.000126

AC XY:

AN XY:

134660

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000277

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000120

AC:

175

AN:

1461694

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000150

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000223

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000470

AC:

ExAC

AF:

0.000116

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.6101G>A (p.R2034Q) alteration is located in exon 42 (coding exon 41) of the MYO18A gene. This alteration results from a G to A substitution at nucleotide position 6101, causing the arginine (R) at amino acid position 2034 to be replaced by a glutamine (Q). 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

Benign

0.072

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.26

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.019

T;.;.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.072

LIST_S2

Uncertain

0.91

D;D;D;D

M_CAP

Benign

0.040

MetaRNN

Benign

0.082

T;T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.1

L;.;.;.

MutationTaster

Benign

0.93

N;N;N;N;D;D

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.42

N;N;N;.

REVEL

Benign

0.22

Sift

Pathogenic

0.0

D;D;D;.

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.30

B;B;B;.

Vest4

0.065

MVP

0.69

MPC

0.31

ClinPred

0.13

GERP RS

2.4

Varity_R

0.12

gMVP

0.36

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

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