chr5-91375516-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_020801.4(ARRDC3):​c.608C>A​(p.Thr203Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ARRDC3
NM_020801.4 missense

Scores

6
6
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.782

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ARRDC3NM_020801.4 linkuse as main transcriptc.608C>A p.Thr203Asn missense_variant 4/8 ENST00000265138.4 NP_065852.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ARRDC3ENST00000265138.4 linkuse as main transcriptc.608C>A p.Thr203Asn missense_variant 4/81 NM_020801.4 ENSP00000265138 P1
ARRDC3ENST00000514284.5 linkuse as main transcriptn.347C>A non_coding_transcript_exon_variant 3/44
ARRDC3ENST00000503192.5 linkuse as main transcript downstream_gene_variant 4
ARRDC3ENST00000508948.5 linkuse as main transcript downstream_gene_variant 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 02, 2023The c.608C>A (p.T203N) alteration is located in exon 4 (coding exon 4) of the ARRDC3 gene. This alteration results from a C to A substitution at nucleotide position 608, causing the threonine (T) at amino acid position 203 to be replaced by an asparagine (N). 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
0.94
BayesDel_addAF
Benign
-0.082
T
BayesDel_noAF
Benign
-0.35
CADD
Pathogenic
31
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
T
Eigen
Pathogenic
0.90
Eigen_PC
Pathogenic
0.88
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.046
D
MetaRNN
Pathogenic
0.78
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Uncertain
-3.1
D
REVEL
Uncertain
0.36
Sift
Uncertain
0.0070
D
Sift4G
Uncertain
0.0070
D
Polyphen
1.0
D
Vest4
0.82
MutPred
0.72
Loss of phosphorylation at T203 (P = 0.0253);
MVP
0.31
MPC
1.5
ClinPred
0.98
D
GERP RS
5.5
Varity_R
0.62
gMVP
0.76

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: chr5-90671333; API