X-70270131-A-T

Variant names:

• chrX-70270131-A-T
• rs11548182
• NM_004312.3:c.132A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004312.3(ARR3):​c.132A>T​(p.Leu44Phe) variant causes a missense 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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency: Genomes: not found (cov: 23)
• Consequence: ARR3 NM_004312.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

Genes affected

ARR3 (HGNC:710): (arrestin 3) The protein encoded by this gene is a non-visual arrestin which binds to agonist-activated, phosphorylated G protein-coupled receptors. This binding uncouples the receptor from the heterotrimeric G protein, resulting in termination of the G protein-coupled receptor signaling. The encoded protein also is a part of the centrosome, interacting with gamma-tubulin to help regulate proper centrosome function. [provided by RefSeq, May 2016]

ACMG classification

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=0.2937414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARR3	NM_004312.3	c.132A>T	p.Leu44Phe	missense_variant	Exon 5 of 17	ENST00000307959.9	NP_004303.2
ARR3	XM_047442105.1	c.156A>T	p.Leu52Phe	missense_variant	Exon 4 of 16		XP_047298061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARR3	ENST00000307959.9	c.132A>T	p.Leu44Phe	missense_variant	Exon 5 of 17	1	NM_004312.3	ENSP00000311538.8
ARR3	ENST00000374495.7	c.132A>T	p.Leu44Phe	missense_variant	Exon 5 of 16	1		ENSP00000363619.3
ARR3	ENST00000480877	c.-22A>T		5_prime_UTR_variant	Exon 5 of 8	5		ENSP00000425505.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	.;.;T
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.;L
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.6	D;.;D
REVEL	Benign	0.10
Sift	Benign	0.060	T;.;T
Sift4G	Uncertain	0.041	D;D;D
Polyphen		0.080	B;.;P
Vest4		0.38
MutPred		0.21		Gain of catalytic residue at L44 (P = 0.0174);Gain of catalytic residue at L44 (P = 0.0174);Gain of catalytic residue at L44 (P = 0.0174);
MVP		0.61
MPC		0.33
ClinPred		0.50	D
GERP RS		0.45
Varity_R		0.18
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs11548182; hg19: chrX-69489981;