1-8360242-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001042681.2(RERE):c.3265C>T(p.Pro1089Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,429,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1089A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RERE
NM_001042681.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.99

Publications

1 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

RERE links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2364636).

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
RERE	NM_001042681.2	MANE Select	c.3265C>T	p.Pro1089Ser	missense	Exon 18 of 23	NP_001036146.1
RERE	NM_012102.4		c.3265C>T	p.Pro1089Ser	missense	Exon 19 of 24	NP_036234.3
RERE	NM_001042682.2		c.1603C>T	p.Pro535Ser	missense	Exon 8 of 13	NP_001036147.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RERE	ENST00000400908.7	TSL:1 MANE Select	c.3265C>T	p.Pro1089Ser	missense	Exon 18 of 23	ENSP00000383700.2
RERE	ENST00000337907.7	TSL:1	c.3265C>T	p.Pro1089Ser	missense	Exon 19 of 24	ENSP00000338629.3
RERE	ENST00000476556.5	TSL:1	c.1603C>T	p.Pro535Ser	missense	Exon 8 of 13	ENSP00000422246.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000537

AC:

AN:

186072

AF XY:

0.00000981

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000338

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000210

AC:

AN:

1429394

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

708172

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32958

American (AMR)

AF:

0.0000244

AC:

AN:

41062

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25452

East Asian (EAS)

AF:

0.00

AC:

AN:

38262

South Asian (SAS)

AF:

0.0000122

AC:

AN:

82066

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48228

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5522

European-Non Finnish (NFE)

AF:

9.12e-7

AC:

AN:

1096770

Other (OTH)

AF:

0.00

AC:

AN:

59074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.083

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.79

M_CAP

Benign

0.030

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.0

PhyloP100

8.0

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-2.0

REVEL

Benign

0.15

Sift

Uncertain

0.016

Sift4G

Benign

0.19

Polyphen

0.28

Vest4

0.46

MutPred

0.52

Gain of helix (P = 0.0496)

MVP

0.14

MPC

0.36

ClinPred

0.48

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.090

gMVP

0.33

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over