Genetic Variant ARL6IP6:p.Leu121Phe (chr2-152718985-C-T) – 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.361C>T(p.Leu121Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L121I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ARL6IP6
NM_152522.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.08

Publications

0 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:

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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=0.26638818).

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.361C>T	p.Leu121Phe	missense	Exon 1 of 4	NP_689735.1	Q8N6S5
ARL6IP6	NM_001371972.1		c.361C>T	p.Leu121Phe	missense	Exon 1 of 4	NP_001358901.1	A0A8I5KQ30
ARL6IP6	NM_001350068.2		c.-400C>T		5_prime_UTR	Exon 1 of 4	NP_001336997.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARL6IP6	ENST00000326446.10	TSL:1 MANE Select	c.361C>T	p.Leu121Phe	missense	Exon 1 of 4	ENSP00000315357.5	Q8N6S5
ARL6IP6	ENST00000692399.1		c.361C>T	p.Leu121Phe	missense	Exon 1 of 3	ENSP00000510087.1	A0A8I5KU55
ARL6IP6	ENST00000686080.1		c.361C>T	p.Leu121Phe	missense	Exon 1 of 4	ENSP00000509648.1	A0A8I5KQ30

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1433522

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709416

African (AFR)

AF:

0.00

AC:

AN:

32490

American (AMR)

AF:

0.00

AC:

AN:

41186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25320

East Asian (EAS)

AF:

0.00

AC:

AN:

38682

South Asian (SAS)

AF:

0.00

AC:

AN:

82986

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5666

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1095356

Other (OTH)

AF:

0.00

AC:

AN:

59108

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.041

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.68

M_CAP

Benign

0.015

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.9

PhyloP100

1.1

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.1

REVEL

Benign

0.11

Sift

Benign

0.070

Sift4G

Benign

0.11

Polyphen

0.89

Vest4

0.39

MutPred

0.35

Loss of stability (P = 0.5583)

MVP

0.52

MPC

0.79

ClinPred

0.53

GERP RS

1.8

PromoterAI

0.022

Neutral

(source)

Varity_R

0.063

gMVP

0.41

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over