chr5-91371444-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_020801.4(ARRDC3):ā€‹c.1201C>Gā€‹(p.Pro401Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

ARRDC3
NM_020801.4 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.94
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.24605429).
BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ARRDC3NM_020801.4 linkuse as main transcriptc.1201C>G p.Pro401Ala missense_variant 8/8 ENST00000265138.4 NP_065852.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ARRDC3ENST00000265138.4 linkuse as main transcriptc.1201C>G p.Pro401Ala missense_variant 8/81 NM_020801.4 ENSP00000265138 P1
ARRDC3ENST00000511391.1 linkuse as main transcriptn.175C>G non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
250626
Hom.:
0
AF XY:
0.0000369
AC XY:
5
AN XY:
135454
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000381
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1460922
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
726786
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
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
Bravo
AF:
0.0000151
ExAC
AF:
0.0000247
AC:
3

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 GeneticsJan 18, 2023The c.1201C>G (p.P401A) alteration is located in exon 8 (coding exon 8) of the ARRDC3 gene. This alteration results from a C to G substitution at nucleotide position 1201, causing the proline (P) at amino acid position 401 to be replaced by an alanine (A). 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
0.19
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.31
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.27
T
Eigen
Uncertain
0.62
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.25
T
MetaSVM
Benign
-1.2
T
MutationAssessor
Benign
1.9
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.55
T
PROVEAN
Uncertain
-3.9
D
REVEL
Benign
0.24
Sift
Uncertain
0.016
D
Sift4G
Uncertain
0.027
D
Polyphen
0.89
P
Vest4
0.56
MutPred
0.34
Loss of stability (P = 0.0591);
MVP
0.14
MPC
1.3
ClinPred
0.49
T
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.27
gMVP
0.58

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs765625079; hg19: chr5-90667261; API