rs1259871272

chr1-8360242-G-Achr1-8360242-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.99

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2364636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RERE	NM_001042681.2	c.3265C>T	p.Pro1089Ser	missense_variant	18/23	ENST00000400908.7
RERE	NM_012102.4	c.3265C>T	p.Pro1089Ser	missense_variant	19/24
RERE	NM_001042682.2	c.1603C>T	p.Pro535Ser	missense_variant	8/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RERE	ENST00000400908.7	c.3265C>T	p.Pro1089Ser	missense_variant	18/23	1	NM_001042681.2	P1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD3 exomes AF: 0.00000537 AC: 1 AN: 186072 Hom.: 0 AF XY: 0.00000981 AC XY: 1 AN XY: 101970

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 SAS 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: 3 AN: 1429394 Hom.: 0 Cov.: 36 AF XY: 0.00000282 AC XY: 2 AN XY: 708172

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000244

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000122

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.12e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.;.;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.083
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.0	M;.;.;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.016	D;D;T;D
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.28	B;B;.;B
Vest4		0.46
MutPred		0.52		Gain of helix (P = 0.0496);.;.;Gain of helix (P = 0.0496);
MVP		0.14
MPC		0.36
ClinPred		0.48	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.090
gMVP		0.33

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

LitVar

Other links and lift over

dbSNP: rs1259871272; hg19: chr1-8420302; COSMIC: COSV104646059; COSMIC: COSV104646059;