17-29111451-G-T

Variant names:

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

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_078471.4(MYO18A):​c.2873C>A​(p.Ala958Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.958

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18A	NM_078471.4	c.2873C>A	p.Ala958Asp	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	c.2873C>A	p.Ala958Asp	missense_variant	Exon 17 of 42	1	NM_078471.4	ENSP00000437073.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.80	D;.;.;T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.96	D;D;D;D
MetaSVM	Uncertain	0.67	D
MutationAssessor	Uncertain	2.6	M;M;M;.
PhyloP100		9.6
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-5.4	D;D;D;.
REVEL	Pathogenic	0.94
Sift	Uncertain	0.0010	D;D;D;.
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.92
MutPred		0.72		Gain of disorder (P = 0.0537);Gain of disorder (P = 0.0537);Gain of disorder (P = 0.0537);.;
MVP		0.88
MPC		1.1
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.90
gMVP		0.92

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;