1-8359846-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_001042681.2(RERE):c.3536G>A(p.Arg1179Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,610,856 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1179L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

RERE
NM_001042681.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 6.09

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder with or without congenital anomalies
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
neurodevelopmental disorder with or without anomalies of the brain, eye, or heart
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

RERE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27490008).

BS2

High AC in GnomAd4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042681.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RERE	NM_001042681.2	MANE Select	c.3536G>A	p.Arg1179Gln	missense	Exon 19 of 23	NP_001036146.1	Q9P2R6-1
RERE	NM_012102.4		c.3536G>A	p.Arg1179Gln	missense	Exon 20 of 24	NP_036234.3
RERE	NM_001042682.2		c.1874G>A	p.Arg625Gln	missense	Exon 9 of 13	NP_001036147.1	Q9P2R6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RERE	ENST00000400908.7	TSL:1 MANE Select	c.3536G>A	p.Arg1179Gln	missense	Exon 19 of 23	ENSP00000383700.2	Q9P2R6-1
RERE	ENST00000337907.7	TSL:1	c.3536G>A	p.Arg1179Gln	missense	Exon 20 of 24	ENSP00000338629.3	Q9P2R6-1
RERE	ENST00000476556.5	TSL:1	c.1874G>A	p.Arg625Gln	missense	Exon 9 of 13	ENSP00000422246.1	Q9P2R6-2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000241

AC:

AN:

248700

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1458622

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

725798

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000360

AC:

AN:

1111888

Other (OTH)

AF:

0.0000497

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41554

American (AMR)

AF:

0.000131

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000194

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68012

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000347

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.014

MetaRNN

Benign

0.27

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

6.1

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-2.0

REVEL

Benign

0.21

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.025

Polyphen

1.0

Vest4

0.59

MVP

0.67

MPC

0.41

ClinPred

0.30

GERP RS

5.4

Varity_R

0.27

gMVP

0.31

Mutation Taster

=63/37

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over