17-29074043-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_078471.4(MYO18A):c.*727G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00339 in 1,614,056 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (84 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (75 hom.)
• Consequence: MYO18A NM_078471.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00100

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024380088).
• BP6: Variant 17-29074043-C-T is Benign according to our data. Variant chr17-29074043-C-T is described in ClinVar as [Benign]. Clinvar id is 768864.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.062 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO18A	NM_078471.4	c.*727G>A		3_prime_UTR_variant	42/42	ENST00000527372.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO18A	ENST00000527372.7	c.*727G>A		3_prime_UTR_variant	42/42	1	NM_078471.4	A1

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2793 AN: 152082 Hom.: 84 Cov.: 32

Gnomad AFR AF: 0.0640

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00642

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.00491 AC: 1223 AN: 248902 Hom.: 37 AF XY: 0.00363 AC XY: 489 AN XY: 134750

Gnomad AFR exome AF: 0.0665

Gnomad AMR exome AF: 0.00338

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000989

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00182 AC: 2663 AN: 1461856 Hom.: 75 Cov.: 30 AF XY: 0.00151 AC XY: 1095 AN XY: 727230

Gnomad4 AFR exome AF: 0.0654

Gnomad4 AMR exome AF: 0.00367

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000220

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000351

Gnomad4 OTH exome AF: 0.00389

GnomAD4 genome AF: 0.0184 AC: 2801 AN: 152200 Hom.: 84 Cov.: 32 AF XY: 0.0183 AC XY: 1360 AN XY: 74410

Gnomad4 AFR AF: 0.0640

Gnomad4 AMR AF: 0.00641

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00333 Hom.: 31

Bravo AF: 0.0209

ESP6500AA AF: 0.0622 AC: 274

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00600 AC: 728

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	2.9
Dann	Benign	0.48
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.30	T
Sift4G	Benign	0.32	T
Polyphen		0.55	P
Vest4		0.12
MVP		0.014
MPC		0.21
ClinPred		0.016	T
GERP RS		-0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.29
gMVP		0.011

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: rs73986791; hg19: chr17-27401061;