1-8359846-C-G

Position:

• chr1-8359846-C-G

Variant summary

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

The NM_001042681.2(RERE):​c.3536G>C​(p.Arg1179Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R1179L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: RERE NM_001042681.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.09

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]

ACMG classification

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/exons	MANE	Protein	UniProt
RERE	NM_001042681.2	c.3536G>C	p.Arg1179Pro	missense_variant	19/23	ENST00000400908.7	NP_001036146.1
RERE	NM_012102.4	c.3536G>C	p.Arg1179Pro	missense_variant	20/24		NP_036234.3
RERE	NM_001042682.2	c.1874G>C	p.Arg625Pro	missense_variant	9/13		NP_001036147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RERE	ENST00000400908.7	c.3536G>C	p.Arg1179Pro	missense_variant	19/23	1	NM_001042681.2	ENSP00000383700.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Benign	0.0065	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D;.;.;D
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	.;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.69	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.73	N;.;.;N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-4.1	D;D;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Benign	0.11	T;T;T;T
Polyphen		1.0	D;.;.;D
Vest4		0.75
MutPred		0.55		Loss of MoRF binding (P = 0.0031);.;.;Loss of MoRF binding (P = 0.0031);
MVP		0.44
MPC		0.52
ClinPred		0.96	D
GERP RS		5.4
Varity_R		0.81
gMVP		0.43

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

LitVar

Other links and lift over

dbSNP: rs150925051; hg19: chr1-8419906;