1-8355453-C-T

Variant summary

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

The NM_001042681.2(RERE):​c.4633G>A​(p.Gly1545Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,612,994 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RERE
NM_001042681.2 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.05
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank MANE Protein UniProt
RERENM_001042681.2 linkc.4633G>A p.Gly1545Ser missense_variant Exon 22 of 23 ENST00000400908.7 NP_001036146.1 Q9P2R6-1
RERENM_012102.4 linkc.4633G>A p.Gly1545Ser missense_variant Exon 23 of 24 NP_036234.3 Q9P2R6-1
RERENM_001042682.2 linkc.2971G>A p.Gly991Ser missense_variant Exon 12 of 13 NP_001036147.1 Q9P2R6-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
REREENST00000400908.7 linkc.4633G>A p.Gly1545Ser missense_variant Exon 22 of 23 1 NM_001042681.2 ENSP00000383700.2 Q9P2R6-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152198
Hom.:
0
Cov.:
33
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
GnomAD3 exomes
AF:
0.00000410
AC:
1
AN:
243618
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
132358
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:
0.00000933
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1460796
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726688
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152198
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Jan 26, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.4633G>A (p.G1545S) alteration is located in exon 23 (coding exon 21) of the RERE gene. This alteration results from a G to A substitution at nucleotide position 4633, causing the glycine (G) at amino acid position 1545 to be replaced by a serine (S). 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
0.082
BayesDel_addAF
Uncertain
0.047
T
BayesDel_noAF
Benign
-0.17
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T;.;.;.;T
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.95
.;D;D;D;D
M_CAP
Benign
0.037
D
MetaRNN
Uncertain
0.58
D;D;D;D;D
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.9
L;.;.;.;L
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-1.3
N;N;N;N;N
REVEL
Benign
0.15
Sift
Benign
0.23
T;T;T;T;T
Sift4G
Benign
0.29
T;T;T;T;T
Polyphen
0.69
P;.;.;.;P
Vest4
0.71
MutPred
0.50
Loss of relative solvent accessibility (P = 0.0071);.;.;.;Loss of relative solvent accessibility (P = 0.0071);
MVP
0.54
MPC
0.35
ClinPred
0.50
T
GERP RS
6.0
Varity_R
0.11
gMVP
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs1266215006; hg19: chr1-8415513; API