chr17-43400018-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000320033.5(ARL4D):​c.286G>A​(p.Gly96Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,794 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: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ARL4D
ENST00000320033.5 missense

Scores

10
7
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.95
Variant links:
Genes affected
ARL4D (HGNC:656): (ADP ribosylation factor like GTPase 4D) ADP-ribosylation factor 4D is a member of the ADP-ribosylation factor family of GTP-binding proteins. ARL4D is closely similar to ARL4A and ARL4C and each has a nuclear localization signal and an unusually high guanine nucleotide exchange rate. This protein may play a role in membrane-associated intracellular trafficking. [provided by RefSeq, Jul 2021]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.908

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ARL4DNM_001661.4 linkuse as main transcriptc.286G>A p.Gly96Ser missense_variant 2/2 ENST00000320033.5 NP_001652.2
ARL4DXM_011524782.3 linkuse as main transcriptc.286G>A p.Gly96Ser missense_variant 2/2 XP_011523084.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ARL4DENST00000320033.5 linkuse as main transcriptc.286G>A p.Gly96Ser missense_variant 2/21 NM_001661.4 ENSP00000322628 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461794
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727196
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

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 submitterclinical testingAmbry GeneticsJun 29, 2023The c.286G>A (p.G96S) alteration is located in exon 2 (coding exon 1) of the ARL4D gene. This alteration results from a G to A substitution at nucleotide position 286, causing the glycine (G) at amino acid position 96 to be replaced by a serine (S). 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
0.75
BayesDel_addAF
Pathogenic
0.43
D
BayesDel_noAF
Pathogenic
0.38
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.30
T
Eigen
Pathogenic
0.83
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.96
D
M_CAP
Uncertain
0.14
D
MetaRNN
Pathogenic
0.91
D
MetaSVM
Pathogenic
0.79
D
MutationAssessor
Uncertain
2.6
M
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-5.0
D
REVEL
Pathogenic
0.77
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0030
D
Polyphen
1.0
D
Vest4
0.88
MutPred
0.66
Gain of phosphorylation at G96 (P = 0.0681);
MVP
0.95
MPC
2.2
ClinPred
1.0
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.91
gMVP
0.97

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: chr17-41477386; COSMIC: COSV60721946; COSMIC: COSV60721946; API