Variant 11-30332977-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_152316.3(ARL14EP):c.538A>C(p.Thr180Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000565 in 1,613,262 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 2 hom. )

Consequence

ARL14EP
NM_152316.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.84

Variant links:

Genes affected

ARL14EP (HGNC:26798): (ADP ribosylation factor like GTPase 14 effector protein) The protein encoded by this gene is an effector protein. It interacts with ADP-ribosylation factor-like 14 [ARL14, also known as ADP-ribosylation factor 7 (ARF7)], beta-actin (ACTB) and actin-based motor protein myosin 1E (MYO1E). ARL14 is a small GTPase; it controls the export of major histocompatibility class II molecules by connecting to the actin network via this effector protein. [provided by RefSeq, Sep 2014]

ARL14EP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032995343).

BP6

Variant 11-30332977-A-C is Benign according to our data. Variant chr11-30332977-A-C is described in ClinVar as [Benign]. Clinvar id is 709885.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL14EP	NM_152316.3 linkuse as main transcript	c.538A>C	p.Thr180Pro	missense_variant	3/4	ENST00000282032.4	NP_689529.1
ARL14EP	XM_005252792.5 linkuse as main transcript	c.202A>C	p.Thr68Pro	missense_variant	3/4		XP_005252849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ARL14EP	ENST00000282032.4 linkuse as main transcript	c.538A>C	p.Thr180Pro	missense_variant	3/4	1	NM_152316.3	ENSP00000282032	P1
ARL14EP	ENST00000530909.1 linkuse as main transcript			downstream_gene_variant		2		ENSP00000432224
ARL14EP	ENST00000533457.1 linkuse as main transcript			downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00309

AC:

470

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000804

AC:

202

AN:

251098

Hom.:

AF XY:

0.000597

AC XY:

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.0117

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000302

AC:

441

AN:

1460946

Hom.:

Cov.:

AF XY:

0.000281

AC XY:

204

AN XY:

726798

show subpopulations

Gnomad4 AFR exome

AF:

0.0110

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.00309

AC:

470

AN:

152316

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

218

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0107

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000696

Hom.:

Bravo

AF:

0.00359

ESP6500AA

AF:

0.0114

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000997

AC:

121

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.027

DANN

Benign

0.59

DEOGEN2

Benign

0.011

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0033

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.34

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.69

REVEL

Benign

0.083

Sift

Benign

0.32

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.065

MVP

0.11

MPC

0.37

ClinPred

0.020

GERP RS

-11

Varity_R

0.042

gMVP

0.21

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over