5-91383054-A-C

Variant names:

• chr5-91383054-A-C
• NM_020801.4:c.39T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001329672.2(ARRDC3):​c.-474T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARRDC3 NM_001329672.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44

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]

ARRDC3-AS1 (HGNC:44145): (ARRDC3 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22271475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARRDC3	NM_020801.4	c.39T>G	p.Phe13Leu	missense_variant	Exon 1 of 8	ENST00000265138.4	NP_065852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARRDC3	ENST00000265138.4	c.39T>G	p.Phe13Leu	missense_variant	Exon 1 of 8	1	NM_020801.4	ENSP00000265138.3

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

Submissions by phenotype

not specified Uncertain:1

Feb 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.39T>G (p.F13L) alteration is located in exon 1 (coding exon 1) of the ARRDC3 gene. This alteration results from a T to G substitution at nucleotide position 39, causing the phenylalanine (F) at amino acid position 13 to be replaced by a leucine (L). 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	0.92
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Benign	0.86
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.23	N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.25
Sift	Benign	0.45	T
Sift4G	Benign	0.53	T
Polyphen		0.0010	B
Vest4		0.59
MutPred		0.47		Loss of catalytic residue at F13 (P = 0.0109);
MVP		0.66
MPC		0.56
ClinPred		0.35	T
GERP RS		2.9
Varity_R		0.49
gMVP		0.67

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: chr5-90678871;