X-70278629-C-G

Variant names:

• chrX-70278629-C-G
• NM_004312.3:c.893C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004312.3(ARR3):​c.893C>G​(p.Ala298Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000365 in 1,095,907 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000036 (0 hom. 0 hem.)
• Consequence: ARR3 NM_004312.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.39

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.838

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARR3	NM_004312.3	c.893C>G	p.Ala298Gly	missense_variant	Exon 12 of 17	ENST00000307959.9	NP_004303.2
ARR3	XM_047442105.1	c.917C>G	p.Ala306Gly	missense_variant	Exon 11 of 16		XP_047298061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARR3	ENST00000307959.9	c.893C>G	p.Ala298Gly	missense_variant	Exon 12 of 17	1	NM_004312.3	ENSP00000311538.8
ARR3	ENST00000374495.7	c.893C>G	p.Ala298Gly	missense_variant	Exon 12 of 16	1		ENSP00000363619.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000365 AC: 4 AN: 1095907 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 361355

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000476

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	.;.;T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.8	M;.;M
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.7	D;.;D
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D;.;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.57
MutPred		0.85		Gain of disorder (P = 0.0531);Gain of disorder (P = 0.0531);Gain of disorder (P = 0.0531);
MVP		0.50
MPC		0.23
ClinPred		1.0	D
GERP RS		3.6
Varity_R		0.89
gMVP		0.46

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: chrX-69498479;