GeneBe

rs1467880651

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001025595.3(ARFIP1):​c.449G>A​(p.Gly150Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. G150A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ARFIP1
NM_001025595.3 missense

Scores

8
8
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 10.0

Publications

0 publications found
Variant links:
Genes affected
ARFIP1 (HGNC:21496): (ADP ribosylation factor interacting protein 1) Enables phosphatidylinositol-4-phosphate binding activity. Involved in negative regulation of retrograde transport, endosome to Golgi. Acts upstream of or within intracellular protein transport and regulation of protein secretion. Located in Golgi membrane; cytosol; and trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.758

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025595.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ARFIP1
NM_001025595.3
MANE Select
c.449G>Ap.Gly150Asp
missense
Exon 6 of 9NP_001020766.1B4E273
ARFIP1
NM_001287431.2
c.449G>Ap.Gly150Asp
missense
Exon 6 of 9NP_001274360.1B4E273
ARFIP1
NM_001287432.2
c.449G>Ap.Gly150Asp
missense
Exon 7 of 10NP_001274361.1P53367-1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ARFIP1
ENST00000353617.7
TSL:5 MANE Select
c.449G>Ap.Gly150Asp
missense
Exon 6 of 9ENSP00000296557.4P53367-1
ARFIP1
ENST00000451320.6
TSL:1
c.449G>Ap.Gly150Asp
missense
Exon 6 of 9ENSP00000395083.2P53367-1
ARFIP1
ENST00000356064.3
TSL:1
c.353G>Ap.Gly118Asp
missense
Exon 5 of 8ENSP00000348360.3P53367-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
250372
AF XY:
0.00
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.090
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.90
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Benign
0.063
D
MetaRNN
Pathogenic
0.76
D
MetaSVM
Uncertain
0.30
D
MutationAssessor
Uncertain
2.5
M
PhyloP100
10
PrimateAI
Pathogenic
0.87
D
PROVEAN
Uncertain
-4.2
D
REVEL
Uncertain
0.64
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.0050
D
Polyphen
1.0
D
Vest4
0.76
MutPred
0.42
Gain of glycosylation at S151 (P = 0.0151)
MVP
0.94
MPC
1.1
ClinPred
1.0
D
GERP RS
5.5
Varity_R
0.72
gMVP
0.75
Mutation Taster
=43/57
disease causing

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

Other links and lift over

dbSNP: rs1467880651; hg19: chr4-153802152; API