Variant 17-5428147-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001033002.4(RPAIN):c.566A>G(p.His189Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000792 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 0 hom. )

Consequence

RPAIN
NM_001033002.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.88

Variant links:

Genes affected

RPAIN (HGNC:28641): (RPA interacting protein) Predicted to enable metal ion binding activity. Acts upstream of or within several processes, including DNA metabolic process; protein import into nucleus; and response to UV. Located in PML body; cytoplasm; and fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

RPAIN links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07292476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPAIN	NM_001033002.4 linkuse as main transcript	c.566A>G	p.His189Arg	missense_variant	6/7	ENST00000381209.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPAIN	ENST00000381209.8 linkuse as main transcript	c.566A>G	p.His189Arg	missense_variant	6/7	1	NM_001033002.4	P1	Q86UA6-1
	ENST00000575890.1 linkuse as main transcript	n.1584-2654T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000499

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000852

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000469

AC:

118

AN:

251474

Hom.:

AF XY:

0.000500

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000924

Gnomad NFE exome

AF:

0.000765

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000823

AC:

1203

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000787

AC XY:

572

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.000955

Gnomad4 NFE exome

AF:

0.000981

Gnomad4 OTH exome

AF:

0.000762

GnomAD4 genome

AF:

0.000499

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.000852

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000691

Hom.:

Bravo

AF:

0.000446

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000461

AC:

EpiCase

AF:

0.000818

EpiControl

AF:

0.000533

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 09, 2022

The c.566A>G (p.H189R) alteration is located in exon 6 (coding exon 6) of the RPAIN gene. This alteration results from a A to G substitution at nucleotide position 566, causing the histidine (H) at amino acid position 189 to be replaced by an arginine (R). 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

Benign

0.099

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.023

T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.067

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.073

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

0.77

D;D;D;D;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.11

Sift

Benign

0.24

T;T

Sift4G

Benign

0.58

T;T

Polyphen

0.21

B;.

Vest4

0.44

MVP

0.55

MPC

0.45

ClinPred

0.039

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.076

gMVP

0.43

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over