NM_001042681.2:c.3248G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001042681.2(RERE):​c.3248G>T​(p.Gly1083Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000635 in 1,574,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 29)
Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

RERE
NM_001042681.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.691

Publications

0 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.04762742).
BS2
High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RERENM_001042681.2 linkc.3248G>T p.Gly1083Val missense_variant Exon 18 of 23 ENST00000400908.7 NP_001036146.1 Q9P2R6-1
RERENM_012102.4 linkc.3248G>T p.Gly1083Val missense_variant Exon 19 of 24 NP_036234.3 Q9P2R6-1
RERENM_001042682.2 linkc.1586G>T p.Gly529Val missense_variant Exon 8 of 13 NP_001036147.1 Q9P2R6-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
REREENST00000400908.7 linkc.3248G>T p.Gly1083Val missense_variant Exon 18 of 23 1 NM_001042681.2 ENSP00000383700.2 Q9P2R6-1

Frequencies

GnomAD3 genomes
AF:
0.00000661
AC:
1
AN:
151336
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000172
AC:
3
AN:
174718
AF XY:
0.0000209
show subpopulations
Gnomad AFR exome
AF:
0.000110
Gnomad AMR exome
AF:
0.0000351
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000141
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000633
AC:
9
AN:
1422808
Hom.:
0
Cov.:
36
AF XY:
0.00000568
AC XY:
4
AN XY:
704468
show subpopulations
African (AFR)
AF:
0.0000305
AC:
1
AN:
32740
American (AMR)
AF:
0.00
AC:
0
AN:
40294
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25348
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37820
South Asian (SAS)
AF:
0.00
AC:
0
AN:
81514
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
47470
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5420
European-Non Finnish (NFE)
AF:
0.00000640
AC:
7
AN:
1093352
Other (OTH)
AF:
0.0000170
AC:
1
AN:
58850
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00000661
AC:
1
AN:
151336
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
73832
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41124
American (AMR)
AF:
0.00
AC:
0
AN:
15200
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5102
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4768
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10540
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
67830
Other (OTH)
AF:
0.00
AC:
0
AN:
2078
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.000244
AC:
1
ESP6500EA
AF:
0.000123
AC:
1
ExAC
AF:
0.0000171
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Sep 13, 2017
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
6.4
DANN
Benign
0.18
DEOGEN2
Benign
0.11
T;.;.;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.80
.;T;T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.048
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.035
N;.;.;N
PhyloP100
0.69
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.83
N;N;N;N
REVEL
Benign
0.016
Sift
Benign
0.20
T;T;T;T
Sift4G
Benign
0.27
T;T;T;T
Polyphen
0.0
B;B;.;B
Vest4
0.089
MVP
0.27
MPC
0.45
ClinPred
0.0055
T
GERP RS
0.89
Varity_R
0.048
gMVP
0.27
Mutation Taster
=89/11
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs370962200; hg19: chr1-8420319; API