Variant 12-15109455-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_032918.3(RERG):c.255C>A(p.Asp85Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RERG
NM_032918.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.59

Variant links:

Genes affected

RERG (HGNC:15980): (RAS like estrogen regulated growth inhibitor) RERG, a member of the RAS superfamily of GTPases, inhibits cell proliferation and tumor formation (Finlin et al., 2001 [PubMed 11533059]).[supplied by OMIM, Mar 2009]

RERG links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.905

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RERG	NM_032918.3 link	c.255C>A	p.Asp85Glu	missense_variant	Exon 5 of 5	ENST00000256953.6	NP_116307.1	Q96A58-1A0A024RAT4
RERG	NM_001190726.2 link	c.198C>A	p.Asp66Glu	missense_variant	Exon 4 of 4		NP_001177655.1	Q96A58-2
RERG	XM_047429797.1 link	c.246C>A	p.Asp82Glu	missense_variant	Exon 5 of 5		XP_047285753.1
RERG	XM_047429798.1 link	c.*109C>A		downstream_gene_variant			XP_047285754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERG	ENST00000256953.6 link	c.255C>A	p.Asp85Glu	missense_variant	Exon 5 of 5	1	NM_032918.3	ENSP00000256953.2		Q96A58-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461770

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.255C>A (p.D85E) alteration is located in exon 5 (coding exon 4) of the RERG gene. This alteration results from a C to A substitution at nucleotide position 255, causing the aspartic acid (D) at amino acid position 85 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

T;T;T;.;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

.;.;D;D;D

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.90

D;D;D;D;D

MetaSVM

Uncertain

0.55

MutationAssessor

Pathogenic

3.5

H;H;H;.;.

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.62

N;N;N;N;N

REVEL

Pathogenic

0.70

Sift

Uncertain

0.011

D;D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;.

Polyphen

0.27

B;B;B;.;.

Vest4

0.77

MutPred

0.84

Loss of phosphorylation at Y84 (P = 0.203);Loss of phosphorylation at Y84 (P = 0.203);Loss of phosphorylation at Y84 (P = 0.203);.;.;

MVP

0.90

MPC

0.55

ClinPred

0.96

GERP RS

5.2

Varity_R

0.56

gMVP

0.79

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over