Genetic Variant NM_152522.7:c.5C>T (chr2-152718629-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM1BP4

The NM_152522.7(ARL6IP6):c.5C>T(p.Ser2Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 1,528,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000073 ( 0 hom. )

Consequence

ARL6IP6
NM_152522.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67

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.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity AR6P6_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.37593132).

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.5C>T	p.Ser2Leu	missense	Exon 1 of 4	NP_689735.1	Q8N6S5
ARL6IP6	NM_001371972.1		c.5C>T	p.Ser2Leu	missense	Exon 1 of 4	NP_001358901.1	A0A8I5KQ30
ARL6IP6	NR_146428.2		n.10C>T		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.5C>T	p.Ser2Leu	missense	Exon 1 of 4	ENSP00000315357.5	Q8N6S5
ARL6IP6	ENST00000692399.1		c.5C>T	p.Ser2Leu	missense	Exon 1 of 3	ENSP00000510087.1	A0A8I5KU55
ARL6IP6	ENST00000686080.1		c.5C>T	p.Ser2Leu	missense	Exon 1 of 4	ENSP00000509648.1	A0A8I5KQ30

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000163

AC:

AN:

184284

AF XY:

0.0000100

show subpopulations

Gnomad AFR exome

AF:

0.000224

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000727

AC:

AN:

1376382

Hom.:

Cov.:

AF XY:

0.00000444

AC XY:

AN XY:

675594

show subpopulations

African (AFR)

AF:

0.000131

AC:

AN:

30606

American (AMR)

AF:

0.00

AC:

AN:

32306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21078

East Asian (EAS)

AF:

0.00

AC:

AN:

38314

South Asian (SAS)

AF:

0.00

AC:

AN:

73144

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49718

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5174

European-Non Finnish (NFE)

AF:

0.00000468

AC:

AN:

1069414

Other (OTH)

AF:

0.0000177

AC:

AN:

56628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.0000657

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2094

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

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:

0.00

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000167

AC:

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

Uncertain

0.39

BayesDel_addAF

Benign

-0.0096

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.47

M_CAP

Benign

0.049

MetaRNN

Benign

0.38

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

1.9

PhyloP100

3.7

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.52

MutPred

0.31

Loss of phosphorylation at S2 (P = 0.0096)

MVP

0.57

MPC

0.77

ClinPred

0.69

GERP RS

4.0

PromoterAI

0.68

Over-expression

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.25

gMVP

0.26

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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