Variant 1-8360443-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001042681.2(RERE):c.3064C>A(p.Pro1022Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000043 ( 0 hom., cov: 17)

Exomes 𝑓: 0.000056 ( 1 hom. )

Consequence

RERE
NM_001042681.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.67

Variant links:

Genes affected

RERE (HGNC:9965): (arginine-glutamic acid dipeptide repeats) This gene encodes a member of the atrophin family of arginine-glutamic acid (RE) dipeptide repeat-containing proteins. The encoded protein co-localizes with a transcription factor in the nucleus, and its overexpression triggers apoptosis. A similar protein in mouse associates with histone deacetylase and is thought to function as a transcriptional co-repressor during embryonic development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RERE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.037635326).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RERE	NM_001042681.2 linkuse as main transcript	c.3064C>A	p.Pro1022Thr	missense_variant	18/23	ENST00000400908.7	NP_001036146.1
RERE	NM_012102.4 linkuse as main transcript	c.3064C>A	p.Pro1022Thr	missense_variant	19/24		NP_036234.3
RERE	NM_001042682.2 linkuse as main transcript	c.1402C>A	p.Pro468Thr	missense_variant	8/13		NP_001036147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RERE	ENST00000400908.7 linkuse as main transcript	c.3064C>A	p.Pro1022Thr	missense_variant	18/23	1	NM_001042681.2	ENSP00000383700	P1	Q9P2R6-1

Frequencies

GnomAD3 genomes

AF:

0.0000429

AC:

AN:

139780

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000540

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000704

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000218

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000313

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000781

AC:

AN:

38408

Hom.:

AF XY:

0.000150

AC XY:

AN XY:

19994

show subpopulations

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000210

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000560

AC:

AN:

821502

Hom.:

Cov.:

AF XY:

0.0000637

AC XY:

AN XY:

408144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000171

Gnomad4 SAS exome

AF:

0.000102

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000543

Gnomad4 OTH exome

AF:

0.0000535

GnomAD4 genome

AF:

0.0000429

AC:

AN:

139874

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

67780

show subpopulations

Gnomad4 AFR

AF:

0.0000539

Gnomad4 AMR

AF:

0.0000703

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000219

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000313

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000211

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.17

DEOGEN2

Benign

0.16

T;.;.;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.99

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.75

.;T;T;T

M_CAP

Benign

0.046

MetaRNN

Benign

0.038

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;.;.;L

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Benign

0.096

Sift

Benign

0.26

T;T;T;T

Sift4G

Uncertain

0.015

D;D;D;D

Polyphen

0.0

B;B;.;B

Vest4

0.19

MutPred

0.37

Loss of catalytic residue at P1021 (P = 0.0191);.;.;Loss of catalytic residue at P1021 (P = 0.0191);

MVP

0.45

MPC

0.40

ClinPred

0.074

GERP RS

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.044

gMVP

0.28

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over