chr5-91375055-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_020801.4(ARRDC3):āc.737T>Cā(p.Leu246Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,092 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 (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 33)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
ARRDC3
NM_020801.4 missense
NM_020801.4 missense
Scores
7
4
8
Clinical Significance
Conservation
PhyloP100: 9.29
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, 0.807
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARRDC3 | NM_020801.4 | c.737T>C | p.Leu246Pro | missense_variant | 5/8 | ENST00000265138.4 | NP_065852.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ARRDC3 | ENST00000265138.4 | c.737T>C | p.Leu246Pro | missense_variant | 5/8 | 1 | NM_020801.4 | ENSP00000265138 | P1 | |
ARRDC3 | ENST00000505631.1 | n.290T>C | non_coding_transcript_exon_variant | 1/2 | 2 | |||||
ARRDC3 | ENST00000514284.5 | n.476T>C | non_coding_transcript_exon_variant | 4/4 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152212Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461880Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727244
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74362
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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 submitter | clinical testing | Ambry Genetics | Jun 21, 2021 | The c.737T>C (p.L246P) alteration is located in exon 5 (coding exon 5) of the ARRDC3 gene. This alteration results from a T to C substitution at nucleotide position 737, causing the leucine (L) at amino acid position 246 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at