Variant 20-63700638-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001267547.3(ARFRP1):c.482G>A(p.Arg161Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000435 in 1,610,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ARFRP1
NM_001267547.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.61

Variant links:

Genes affected

ARFRP1 (HGNC:662): (ADP ribosylation factor related protein 1) The protein encoded by this gene is a membrane-associated GTP-ase which localizes to the plasma membrane and is related to the ADP-ribosylation factor (ARF) and ARF-like (ARL) proteins. This gene plays a role in membrane trafficking between the trans-Golgi network and endosomes. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, May 2012]

ARFRP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.949

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARFRP1	NM_001267547.3 linkuse as main transcript	c.482G>A	p.Arg161Gln	missense_variant	7/8	ENST00000622789.5	NP_001254476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARFRP1	ENST00000622789.5 linkuse as main transcript	c.482G>A	p.Arg161Gln	missense_variant	7/8	1	NM_001267547.3	ENSP00000483486	P1	Q13795-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1458398

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725494

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2023

The c.482G>A (p.R161Q) alteration is located in exon 7 (coding exon 6) of the ARFRP1 gene. This alteration results from a G to A substitution at nucleotide position 482, causing the arginine (R) at amino acid position 161 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Uncertain

0.067

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.74

.;D;D;D;.;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

.;.;D;.;D;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.95

D;D;D;D;D;D

MetaSVM

Uncertain

0.22

MutationAssessor

Pathogenic

3.0

.;M;M;M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.61

Sift4G

Uncertain

0.053

T;T;T;T;T;T

Polyphen

1.0

.;D;D;D;.;.

Vest4

0.88

MutPred

0.79

.;Loss of catalytic residue at R161 (P = 0.0605);Loss of catalytic residue at R161 (P = 0.0605);Loss of catalytic residue at R161 (P = 0.0605);Loss of catalytic residue at R161 (P = 0.0605);.;

MVP

0.63

ClinPred

0.98

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.83

gMVP

0.67

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

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