17-29129237-G-C

Position:

• chr17-29129237-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_078471.4(MYO18A):​c.1000-6984C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 371,892 control chromosomes in the GnomAD database, including 38,152 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 (16075 hom., cov: 32)
  • Exomes 𝑓: 0.45 (22077 hom.)
• Consequence: MYO18A NM_078471.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO18A	NM_078471.4	c.1000-6984C>G		intron_variant		ENST00000527372.7	NP_510880.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO18A	ENST00000527372.7	c.1000-6984C>G		intron_variant		1	NM_078471.4	ENSP00000437073	A1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68803 AN: 151846 Hom.: 16068 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: 0.851

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.466

GnomAD4 exome AF: 0.445 AC: 97873 AN: 219928 Hom.: 22077 AF XY: 0.446 AC XY: 46775 AN XY: 104956

Gnomad4 AFR exome AF: 0.417

Gnomad4 AMR exome AF: 0.406

Gnomad4 ASJ exome AF: 0.564

Gnomad4 EAS exome AF: 0.855

Gnomad4 SAS exome AF: 0.471

Gnomad4 FIN exome AF: 0.574

Gnomad4 NFE exome AF: 0.441

Gnomad4 OTH exome AF: 0.478

GnomAD4 genome AF: 0.453 AC: 68852 AN: 151964 Hom.: 16075 Cov.: 32 AF XY: 0.452 AC XY: 33569 AN XY: 74276

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.470

Alfa AF: 0.285 Hom.: 674

Bravo AF: 0.452

Asia WGS AF: 0.640 AC: 2225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.59
DANN	Benign	0.60

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: rs11080078; hg19: chr17-27456255;