rs1035063066

chr1-8360947-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001042681.2(RERE):c.2560C>T(p.Pro854Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: RERE NM_001042681.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27011016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RERE	NM_001042681.2	c.2560C>T	p.Pro854Ser	missense_variant	18/23	ENST00000400908.7
RERE	NM_012102.4	c.2560C>T	p.Pro854Ser	missense_variant	19/24
RERE	NM_001042682.2	c.898C>T	p.Pro300Ser	missense_variant	8/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RERE	ENST00000400908.7	c.2560C>T	p.Pro854Ser	missense_variant	18/23	1	NM_001042681.2	P1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152028 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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 AF: 0.00000229 AC: 3 AN: 1308662 Hom.: 0 Cov.: 35 AF XY: 0.00000156 AC XY: 1 AN XY: 639616

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: 0.00000287

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152028 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74254

Gnomad4 AFR AF: 0.0000242

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: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.;.;T
Eigen	Benign	0.10
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.80	D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.4	M;.;.;M
MutationTaster	Benign	0.98	D;D;D;D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.8	D;D;D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0060	D;D;T;D
Sift4G	Uncertain	0.025	D;T;D;D
Polyphen		0.39	B;P;.;B
Vest4		0.28
MutPred		0.60		Gain of phosphorylation at P854 (P = 0.0223);.;.;Gain of phosphorylation at P854 (P = 0.0223);
MVP		0.38
MPC		0.36
ClinPred		0.79	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.20
gMVP		0.40

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: rs1035063066; hg19: chr1-8421007; COSMIC: COSV61949968; COSMIC: COSV61949968;