chr5-91373725-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020801.4(ARRDC3):​c.1147A>G​(p.Ile383Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ARRDC3
NM_020801.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.27
Variant links:
Genes affected
ARRDC3 (HGNC:29263): (arrestin domain containing 3) This gene encodes a member of the arrestin family of proteins, which regulate G protein-mediated signaling. The encoded protein is thought to act as a regulator of breast cancer growth and progression by binding to a phosphorylated form of integrin beta4, a tumor-related antigen, targeting the integrin for internalization and degradation. [provided by RefSeq, Jul 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3280178).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ARRDC3NM_020801.4 linkuse as main transcriptc.1147A>G p.Ile383Val missense_variant 7/8 ENST00000265138.4 NP_065852.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ARRDC3ENST00000265138.4 linkuse as main transcriptc.1147A>G p.Ile383Val missense_variant 7/81 NM_020801.4 ENSP00000265138 P1
ARRDC3ENST00000511391.1 linkuse as main transcriptn.121A>G non_coding_transcript_exon_variant 1/22

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

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 GeneticsApr 26, 2024The c.1147A>G (p.I383V) alteration is located in exon 7 (coding exon 7) of the ARRDC3 gene. This alteration results from a A to G substitution at nucleotide position 1147, causing the isoleucine (I) at amino acid position 383 to be replaced by a valine (V). 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
Benign
0.16
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.53
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.073
T
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.0079
T
MetaRNN
Benign
0.33
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.3
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-0.24
N
REVEL
Benign
0.15
Sift
Benign
0.15
T
Sift4G
Benign
0.48
T
Polyphen
0.80
P
Vest4
0.30
MutPred
0.44
Gain of disorder (P = 0.1551);
MVP
0.23
MPC
0.41
ClinPred
0.64
D
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.11
gMVP
0.39

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: chr5-90669542; API