12-15109184-T-C

Variant names:

• chr12-15109184-T-C
• NM_032918.3:c.526A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032918.3(RERG):​c.526A>G​(p.Lys176Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RERG NM_032918.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.76
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3299178).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RERG	NM_032918.3	c.526A>G	p.Lys176Glu	missense_variant	Exon 5 of 5	ENST00000256953.6	NP_116307.1
RERG	NM_001190726.2	c.469A>G	p.Lys157Glu	missense_variant	Exon 4 of 4		NP_001177655.1
RERG	XM_047429797.1	c.517A>G	p.Lys173Glu	missense_variant	Exon 5 of 5		XP_047285753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERG	ENST00000256953.6	c.526A>G	p.Lys176Glu	missense_variant	Exon 5 of 5	1	NM_032918.3	ENSP00000256953.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.526A>G (p.K176E) alteration is located in exon 5 (coding exon 4) of the RERG gene. This alteration results from a A to G substitution at nucleotide position 526, causing the lysine (K) at amino acid position 176 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	0.71
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T;T;T;.
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	.;.;D;D
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	0.0	N;N;N;.
PhyloP100		7.8
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.92	N;N;N;N
REVEL	Uncertain	0.47
Sift	Benign	0.21	T;T;T;T
Sift4G	Benign	0.36	T;T;T;T
Polyphen		0.64	P;P;P;.
Vest4		0.43
MutPred		0.33		Loss of methylation at K176 (P = 0.0032);Loss of methylation at K176 (P = 0.0032);Loss of methylation at K176 (P = 0.0032);.;
MVP		0.89
MPC		0.71
ClinPred		0.95	D
GERP RS		4.6
Varity_R		0.29
gMVP		0.67
Mutation Taster		=17/83	disease causing

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

Other links and lift over

hg19: chr12-15262118;