Variant 2-152718791-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_152522.7(ARL6IP6):c.167G>T(p.Arg56Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,607,064 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R56G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0082 ( 8 hom., cov: 33)

Exomes 𝑓: 0.011 ( 106 hom. )

Consequence

ARL6IP6
NM_152522.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.40

Variant links:

Genes affected

ARL6IP6 (HGNC:24048): (ADP ribosylation factor like GTPase 6 interacting protein 6) Predicted to be located in nuclear inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARL6IP6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0100771785).

BP6

Variant 2-152718791-G-T is Benign according to our data. Variant chr2-152718791-G-T is described in ClinVar as [Benign]. Clinvar id is 784457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARL6IP6	NM_152522.7 linkuse as main transcript	c.167G>T	p.Arg56Leu	missense_variant	1/4	ENST00000326446.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARL6IP6	ENST00000326446.10 linkuse as main transcript	c.167G>T	p.Arg56Leu	missense_variant	1/4	1	NM_152522.7	P1

Frequencies

GnomAD3 genomes

AF:

0.00816

AC:

1242

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00555

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00793

AC:

1844

AN:

232568

Hom.:

AF XY:

0.00787

AC XY:

1000

AN XY:

126988

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00771

Gnomad ASJ exome

AF:

0.0162

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000680

Gnomad FIN exome

AF:

0.00620

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.0120

GnomAD4 exome

AF:

0.0112

AC:

16257

AN:

1454756

Hom.:

106

Cov.:

AF XY:

0.0108

AC XY:

7831

AN XY:

723270

show subpopulations

Gnomad4 AFR exome

AF:

0.00180

Gnomad4 AMR exome

AF:

0.00850

Gnomad4 ASJ exome

AF:

0.0152

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000587

Gnomad4 FIN exome

AF:

0.00544

Gnomad4 NFE exome

AF:

0.0131

Gnomad4 OTH exome

AF:

0.0100

GnomAD4 genome

AF:

0.00815

AC:

1242

AN:

152308

Hom.:

Cov.:

AF XY:

0.00769

AC XY:

573

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00269

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00555

Gnomad4 NFE

AF:

0.0122

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.00856

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.00160

AC:

ESP6500EA

AF:

0.0122

AC:

104

ExAC

AF:

0.00717

AC:

866

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	ARL6IP6: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.072

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.83

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.9

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.4

REVEL

Benign

0.18

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.015

Polyphen

1.0

Vest4

0.57

MVP

0.59

MPC

0.92

ClinPred

0.030

GERP RS

4.3

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.8

Varity_R

0.28

gMVP

0.33

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