Variant chr1-228097169-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM2PP2PP3_ModeratePP5_Very_Strong

The NM_001658.4(ARF1):c.55C>T(p.Arg19Cys) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ARF1
NM_001658.4 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, multiple submitters, no conflicts P:2

Conservation

PhyloP100: 3.25

Variant links:

Genes affected

ARF1 (HGNC:652): (ADP ribosylation factor 1) ADP-ribosylation factor 1 (ARF1) is a member of the human ARF gene family. The family members encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking as activators of phospholipase D. The gene products, including 6 ARF proteins and 11 ARF-like proteins, constitute a family of the RAS superfamily. The ARF proteins are categorized as class I (ARF1, ARF2 and ARF3), class II (ARF4 and ARF5) and class III (ARF6), and members of each class share a common gene organization. The ARF1 protein is localized to the Golgi apparatus and has a central role in intra-Golgi transport. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ARF1 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 13 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ARF1. . Trascript score misZ 4.1509 (greater than threshold 3.09). GenCC has associacion of gene with periventricular nodular heterotopia, periventricular nodular heterotopia 8.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.922

PP5

Variant 1-228097169-C-T is Pathogenic according to our data. Variant chr1-228097169-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1343801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ARF1	NM_001658.4 linkuse as main transcript	c.55C>T	p.Arg19Cys	missense_variant	2/5	ENST00000272102.10	NP_001649.1
ARF1	NM_001024226.2 linkuse as main transcript	c.55C>T	p.Arg19Cys	missense_variant	2/5		NP_001019397.1
ARF1	NM_001024227.1 linkuse as main transcript	c.55C>T	p.Arg19Cys	missense_variant	2/5		NP_001019398.1
ARF1	NM_001024228.2 linkuse as main transcript	c.55C>T	p.Arg19Cys	missense_variant	2/5		NP_001019399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARF1	ENST00000272102.10 linkuse as main transcript	c.55C>T	p.Arg19Cys	missense_variant	2/5	1	NM_001658.4	ENSP00000272102	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461316

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726926

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Periventricular nodular heterotopia 8

Pathogenic:2

Likely pathogenic, criteria provided, single submitter	clinical testing	Groupe Hospitalier Pitie Salpetriere, UF Genomique du Developpement, Assistance Publique Hopitaux de Paris	Mar 12, 2022	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	Apr 30, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.34

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.44

T;T;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.91

.;.;D

M_CAP

Pathogenic

0.36

MetaRNN

Pathogenic

0.92

D;D;D

MetaSVM

Uncertain

0.75

MutationAssessor

Pathogenic

3.5

H;H;H

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-5.4

D;D;D

REVEL

Pathogenic

0.83

Sift

Uncertain

0.017

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.94

P;P;P

Vest4

0.84

MutPred

0.74

Loss of MoRF binding (P = 0.016);Loss of MoRF binding (P = 0.016);Loss of MoRF binding (P = 0.016);

MVP

0.99

MPC

2.4

ClinPred

0.99

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.67

gMVP

0.96

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over