Genetic Variant ARL6IP6:p.Leu55Val (chr2-152718787-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_152522.7(ARL6IP6):c.163C>G(p.Leu55Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000809 in 1,606,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L55R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

ARL6IP6
NM_152522.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0780

Publications

2 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3422324).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152522.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARL6IP6	NM_152522.7	MANE Select	c.163C>G	p.Leu55Val	missense	Exon 1 of 4	NP_689735.1	Q8N6S5
ARL6IP6	NM_001371972.1		c.163C>G	p.Leu55Val	missense	Exon 1 of 4	NP_001358901.1	A0A8I5KQ30
ARL6IP6	NR_146428.2		n.168C>G		non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARL6IP6	ENST00000326446.10	TSL:1 MANE Select	c.163C>G	p.Leu55Val	missense	Exon 1 of 4	ENSP00000315357.5	Q8N6S5
ARL6IP6	ENST00000692399.1		c.163C>G	p.Leu55Val	missense	Exon 1 of 3	ENSP00000510087.1	A0A8I5KU55
ARL6IP6	ENST00000686080.1		c.163C>G	p.Leu55Val	missense	Exon 1 of 4	ENSP00000509648.1	A0A8I5KQ30

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000430

AC:

AN:

232670

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000962

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000756

AC:

AN:

1454486

Hom.:

Cov.:

AF XY:

0.00000691

AC XY:

AN XY:

723166

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33336

American (AMR)

AF:

0.0000230

AC:

AN:

43434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25956

East Asian (EAS)

AF:

0.00

AC:

AN:

39464

South Asian (SAS)

AF:

0.00

AC:

AN:

85128

European-Finnish (FIN)

AF:

0.0000189

AC:

AN:

52928

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000812

AC:

AN:

1108530

Other (OTH)

AF:

0.00

AC:

AN:

59960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

0.0021

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.77

M_CAP

Benign

0.020

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.9

PhyloP100

-0.078

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.3

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.47

MutPred

0.28

Loss of helix (P = 0.079)

MVP

0.55

MPC

0.82

ClinPred

0.93

GERP RS

-0.61

PromoterAI

0.036

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.8

Varity_R

0.19

gMVP

0.30

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over