NM_078471.4:c.2873C>T

Variant names:

• chr17-29111451-G-A
• rs8076604
• NM_078471.4:c.2873C>T

Variant summary

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

• 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
• Publications: 34 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_078471.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO18A	NM_078471.4	MANE Select	c.2873C>T	p.Ala958Val	missense	Exon 17 of 42	NP_510880.2
	MYO18A	NM_001346765.2		c.2930C>T	p.Ala977Val	missense	Exon 19 of 43	NP_001333694.1
	MYO18A	NM_001346766.2		c.2909C>T	p.Ala970Val	missense	Exon 18 of 42	NP_001333695.1	A0A994J771

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO18A	ENST00000527372.7	TSL:1 MANE Select	c.2873C>T	p.Ala958Val	missense	Exon 17 of 42	ENSP00000437073.1	Q92614-1
	MYO18A	ENST00000533112.5	TSL:1	c.2873C>T	p.Ala958Val	missense	Exon 17 of 40	ENSP00000435932.1	Q92614-3
	MYO18A	ENST00000530254.6	TSL:1	n.*1901C>T		non_coding_transcript_exon	Exon 17 of 41	ENSP00000434817.2	E9PN42

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

GnomAD2 exomes AF: 0.476 AC: 115717 AN: 242890 AF XY: 0.477

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

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

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

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

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 v4.9

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
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.66	N
PhyloP100		9.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.44
Sift	Benign	0.14	T
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.31
MPC		0.92
ClinPred		0.026	T
GERP RS		5.3
Varity_R		0.44
gMVP		0.64
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8076604; hg19: chr17-27438469; COSMIC: COSV106498454; COSMIC: COSV106498454;