Genetic Variant MYO18A:p.Ala958Val (chr17-29111451-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_078471.4(MYO18A):c.2873C>T(p.Ala958Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,610,782 control chromosomes in the GnomAD database, including 173,425 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 0.45 ( 16048 hom., cov: 32)

Exomes 𝑓: 0.46 ( 157377 hom. )

Consequence

MYO18A
NM_078471.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.58

Publications

34 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2875333E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18A	NM_078471.4 link	c.2873C>T	p.Ala958Val	missense_variant	Exon 17 of 42	ENST00000527372.7	NP_510880.2	Q92614-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO18A	ENST00000527372.7 link	c.2873C>T	p.Ala958Val	missense_variant	Exon 17 of 42	1	NM_078471.4	ENSP00000437073.1		Q92614-1

Frequencies

GnomAD3 genomes

AF:

0.453

AC:

68778

AN:

151824

Hom.:

16041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.537

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.555

Gnomad EAS

AF:

0.852

Gnomad SAS

AF:

0.506

Gnomad FIN

AF:

0.425

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.446

Gnomad OTH

AF:

0.464

GnomAD2 exomes

AF:

0.476

AC:

115717

AN:

242890

AF XY:

0.477

show subpopulations

Gnomad AFR exome

AF:

0.414

Gnomad AMR exome

AF:

0.402

Gnomad ASJ exome

AF:

0.553

Gnomad EAS exome

AF:

0.848

Gnomad FIN exome

AF:

0.432

Gnomad NFE exome

AF:

0.448

Gnomad OTH exome

AF:

0.469

GnomAD4 exome

AF:

0.459

AC:

669579

AN:

1458840

Hom.:

157377

Cov.:

AF XY:

0.460

AC XY:

333787

AN XY:

725388

show subpopulations

African (AFR)

AF:

0.417

AC:

13948

AN:

33454

American (AMR)

AF:

0.405

AC:

17861

AN:

44130

Ashkenazi Jewish (ASJ)

AF:

0.557

AC:

14492

AN:

26026

East Asian (EAS)

AF:

0.854

AC:

33835

AN:

39632

South Asian (SAS)

AF:

0.482

AC:

41298

AN:

85758

European-Finnish (FIN)

AF:

0.441

AC:

23482

AN:

53232

Middle Eastern (MID)

AF:

0.467

AC:

2690

AN:

5760

European-Non Finnish (NFE)

AF:

0.444

AC:

493548

AN:

1110582

Other (OTH)

AF:

0.472

AC:

28425

AN:

60266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

20367

40733

61100

81466

101833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15020

30040

45060

60080

75100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.453

AC:

68827

AN:

151942

Hom.:

16048

Cov.:

AF XY:

0.452

AC XY:

33575

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.419

AC:

17338

AN:

41404

American (AMR)

AF:

0.412

AC:

6302

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.555

AC:

1925

AN:

3466

East Asian (EAS)

AF:

0.852

AC:

4391

AN:

5154

South Asian (SAS)

AF:

0.507

AC:

2437

AN:

4808

European-Finnish (FIN)

AF:

0.425

AC:

4489

AN:

10570

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.446

AC:

30333

AN:

67944

Other (OTH)

AF:

0.468

AC:

989

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1871

3741

5612

7482

9353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.456

Hom.:

75846

Bravo

AF:

0.452

TwinsUK

AF:

0.441

AC:

1634

ALSPAC

AF:

0.439

AC:

1690

ESP6500AA

AF:

0.410

AC:

1595

ESP6500EA

AF:

0.446

AC:

3700

ExAC

AF:

0.475

AC:

57394

Asia WGS

AF:

0.638

AC:

2215

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.57

D;.;.;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

T;T;T;T

MetaRNN

Benign

0.0000013

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.66

N;N;N;.

PhyloP100

9.6

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.6

D;D;D;.

REVEL

Uncertain

0.44

Sift

Benign

0.14

T;T;T;.

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.31

MPC

0.92

ClinPred

0.026

GERP RS

5.3

Varity_R

0.44

gMVP

0.64

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over