rs8076604

chr17-29111451-G-Achr17-29111451-G-Cchr17-29111451-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2 BP4_Strong BA1

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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.45 (16048 hom., cov: 32)
  • Exomes 𝑓: 0.46 (157377 hom.)
• Consequence: MYO18A NM_078471.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.58

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• PP2: Missense variant where missense usually causes diseases, MYO18A
• 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/exons	MANE	UniProt
MYO18A	NM_078471.4	c.2873C>T	p.Ala958Val	missense_variant	17/42	ENST00000527372.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO18A	ENST00000527372.7	c.2873C>T	p.Ala958Val	missense_variant	17/42	1	NM_078471.4	A1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68778 AN: 151824 Hom.: 16041 Cov.: 32

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

GnomAD3 exomes AF: 0.476 AC: 115717 AN: 242890 Hom.: 28876 AF XY: 0.477 AC XY: 62817 AN XY: 131794

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 SAS exome AF: 0.483

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.: 60 AF XY: 0.460 AC XY: 333787 AN XY: 725388

Gnomad4 AFR exome AF: 0.417

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.557

Gnomad4 EAS exome AF: 0.854

Gnomad4 SAS exome AF: 0.482

Gnomad4 FIN exome AF: 0.441

Gnomad4 NFE exome AF: 0.444

Gnomad4 OTH exome AF: 0.472

GnomAD4 genome AF: 0.453 AC: 68827 AN: 151942 Hom.: 16048 Cov.: 32 AF XY: 0.452 AC XY: 33575 AN XY: 74262

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.468

Alfa AF: 0.456 Hom.: 40327

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	T
BayesDel_noAF	Uncertain	-0.070
Cadd	Pathogenic	26
Dann	Pathogenic	1.0
DEOGEN2	Uncertain	0.57	D;.;.;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T;T;T;T
MetaRNN	Benign	0.0000013	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.66	N;N;N;.
MutationTaster	Benign	0.0000014	P;P;P;P
PrimateAI	Uncertain	0.61	T
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	T
GERP RS		5.3
Varity_R		0.44
gMVP		0.64

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

Other links and lift over

dbSNP: rs8076604; hg19: chr17-27438469;