chr1-8360361-G-A

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 10P and 1B. PM2PP5_Very_StrongBP4

The NM_001042681.2(RERE):c.3146C>T(p.Pro1049Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 24)

Failed GnomAD Quality Control

Consequence

RERE
NM_001042681.2 missense

Scores

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:2

Conservation

PhyloP100: 7.79

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 1-8360361-G-A is Pathogenic according to our data. Variant chr1-8360361-G-A is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 235329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.28343782). . Strength limited to SUPPORTING due to the PP5.

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.3146C>T	p.Pro1049Leu	missense	Exon 18 of 23	NP_001036146.1
RERE	NM_012102.4		c.3146C>T	p.Pro1049Leu	missense	Exon 19 of 24	NP_036234.3
RERE	NM_001042682.2		c.1484C>T	p.Pro495Leu	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.3146C>T	p.Pro1049Leu	missense	Exon 18 of 23	ENSP00000383700.2
RERE	ENST00000337907.7	TSL:1	c.3146C>T	p.Pro1049Leu	missense	Exon 19 of 24	ENSP00000338629.3
RERE	ENST00000476556.5	TSL:1	c.1484C>T	p.Pro495Leu	missense	Exon 8 of 13	ENSP00000422246.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148854

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

148854

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72558

African (AFR)

AF:

0.00

AC:

AN:

40068

American (AMR)

AF:

0.00

AC:

AN:

14936

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5016

South Asian (SAS)

AF:

0.00

AC:

AN:

4618

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67196

Other (OTH)

AF:

0.00

AC:

AN:

2028

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic/Likely pathogenic

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.0060

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.39

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.038

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.98

MutationAssessor

Benign

2.0

PhyloP100

7.8

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.27

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0080

Polyphen

0.0

Vest4

0.48

MutPred

0.50

Loss of glycosylation at P1049 (P = 0.0273)

MVP

0.55

MPC

0.36

ClinPred

0.96

GERP RS

4.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.28

gMVP

0.39

Mutation Taster

=16/84

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over