chr11-6480002-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001376558.2(ARFIP2):​c.166G>T​(p.Gly56Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ARFIP2
NM_001376558.2 missense

Scores

3
11
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.90
Variant links:
Genes affected
ARFIP2 (HGNC:17160): (ADP ribosylation factor interacting protein 2) Enables several functions, including GTP-dependent protein binding activity; membrane curvature sensor activity; and phosphatidylinositol-4-phosphate binding activity. Involved in actin cytoskeleton organization. Located in cell cortex; ruffle; and trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARFIP2NM_001376558.2 linkc.166G>T p.Gly56Trp missense_variant Exon 3 of 8 ENST00000396777.8 NP_001363487.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARFIP2ENST00000396777.8 linkc.166G>T p.Gly56Trp missense_variant Exon 3 of 8 2 NM_001376558.2 ENSP00000379998.3 P53365-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461884
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
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.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.166G>T (p.G56W) alteration is located in exon 3 (coding exon 2) of the ARFIP2 gene. This alteration results from a G to T substitution at nucleotide position 166, causing the glycine (G) at amino acid position 56 to be replaced by a tryptophan (W). 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
Pathogenic
0.65
BayesDel_addAF
Pathogenic
0.42
D
BayesDel_noAF
Pathogenic
0.36
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
.;T;T;.;T
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.97
D;.;D;D;D
M_CAP
Uncertain
0.20
D
MetaRNN
Uncertain
0.61
D;D;D;D;D
MetaSVM
Benign
-0.39
T
PrimateAI
Uncertain
0.77
T
PROVEAN
Uncertain
-3.5
.;D;D;D;D
REVEL
Uncertain
0.63
Sift
Uncertain
0.0030
.;D;D;D;D
Sift4G
Uncertain
0.0030
D;D;D;D;D
Polyphen
1.0
.;D;D;.;.
Vest4
0.73
MutPred
0.26
Loss of disorder (P = 0.043);Loss of disorder (P = 0.043);Loss of disorder (P = 0.043);.;Loss of disorder (P = 0.043);
MVP
0.91
MPC
1.6
ClinPred
1.0
D
GERP RS
5.1
Varity_R
0.61
gMVP
0.71

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.

Other links and lift over

hg19: chr11-6501232; API