X-70278629-C-T

Position:

• chrX-70278629-C-T

Variant summary

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

The NM_004312.3(ARR3):​c.893C>T​(p.Ala298Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARR3	NM_004312.3	c.893C>T	p.Ala298Val	missense_variant	12/17	ENST00000307959.9	NP_004303.2
ARR3	XM_047442105.1	c.917C>T	p.Ala306Val	missense_variant	11/16		XP_047298061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARR3	ENST00000307959.9	c.893C>T	p.Ala298Val	missense_variant	12/17	1	NM_004312.3	ENSP00000311538	P1
ARR3	ENST00000374495.7	c.893C>T	p.Ala298Val	missense_variant	12/16	1		ENSP00000363619

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000553 AC: 1 AN: 180781 Hom.: 0 AF XY: 0.0000153 AC XY: 1 AN XY: 65337

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000548

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.12e-7 AC: 1 AN: 1095907 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 1 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: 0.0000187

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	0.10
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.36	.;.;T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Pathogenic	3.2	M;.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.7	D;.;D
REVEL	Uncertain	0.50
Sift	Pathogenic	0.0	D;.;D
Sift4G	Uncertain	0.019	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.47
MutPred		0.85		Loss of disorder (P = 0.0688);Loss of disorder (P = 0.0688);Loss of disorder (P = 0.0688);
MVP		0.49
MPC		0.28
ClinPred		0.95	D
GERP RS		3.6
Varity_R		0.85
gMVP		0.68

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

LitVar

Other links and lift over

dbSNP: rs765658563; hg19: chrX-69498479;