Genetic Variant NM_078471.4:c.2873C>T (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

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

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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