Variant 12-15111370-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032918.3(RERG):c.166A>T(p.Met56Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000868 in 1,613,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

RERG
NM_032918.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.09

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.18187195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RERG	NM_032918.3 link	c.166A>T	p.Met56Leu	missense_variant	Exon 4 of 5	ENST00000256953.6	NP_116307.1	Q96A58-1A0A024RAT4
RERG	NM_001190726.2 link	c.109A>T	p.Met37Leu	missense_variant	Exon 3 of 4		NP_001177655.1	Q96A58-2
RERG	XM_047429797.1 link	c.157A>T	p.Met53Leu	missense_variant	Exon 4 of 5		XP_047285753.1
RERG	XM_047429798.1 link	c.330A>T	p.Pro110Pro	synonymous_variant	Exon 5 of 6		XP_047285754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERG	ENST00000256953.6 link	c.166A>T	p.Met56Leu	missense_variant	Exon 4 of 5	1	NM_032918.3	ENSP00000256953.2		Q96A58-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

251016

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1461082

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726892

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 03, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.166A>T (p.M56L) alteration is located in exon 4 (coding exon 3) of the RERG gene. This alteration results from a A to T substitution at nucleotide position 166, causing the methionine (M) at amino acid position 56 to be replaced by a leucine (L). 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

Benign

0.19

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.17

T;T;T;.;.;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.21

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.90

.;.;D;D;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.18

T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-1.5

N;N;N;.;.;.

PrimateAI

Uncertain

0.61

PROVEAN

Benign

0.15

N;N;N;N;N;N

REVEL

Uncertain

0.36

Sift

Benign

0.82

T;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;.;T

Polyphen

0.0

B;B;B;.;.;.

Vest4

0.78

MutPred

0.52

Loss of phosphorylation at T61 (P = 0.1094);Loss of phosphorylation at T61 (P = 0.1094);Loss of phosphorylation at T61 (P = 0.1094);.;.;Loss of phosphorylation at T61 (P = 0.1094);

MVP

0.67

MPC

0.30

ClinPred

0.27

GERP RS

4.1

Varity_R

0.33

gMVP

0.69

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