chr12-15109430-C-G

Variant names:

• chr12-15109430-C-G
• NM_032918.3:c.280G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032918.3(RERG):​c.280G>C​(p.Glu94Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RERG NM_032918.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.10

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RERG	NM_032918.3	c.280G>C	p.Glu94Gln	missense_variant	Exon 5 of 5	ENST00000256953.6	NP_116307.1
RERG	NM_001190726.2	c.223G>C	p.Glu75Gln	missense_variant	Exon 4 of 4		NP_001177655.1
RERG	XM_047429797.1	c.271G>C	p.Glu91Gln	missense_variant	Exon 5 of 5		XP_047285753.1
RERG	XM_047429798.1	c.*134G>C		downstream_gene_variant			XP_047285754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERG	ENST00000256953.6	c.280G>C	p.Glu94Gln	missense_variant	Exon 5 of 5	1	NM_032918.3	ENSP00000256953.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461850 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727232

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T;T;T;.;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	.;.;D;D;D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.49	T;T;T;T;T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.9	L;L;L;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.1	N;N;N;D;N
REVEL	Uncertain	0.39
Sift	Benign	0.12	T;T;T;T;T
Sift4G	Benign	0.16	T;T;T;T;.
Polyphen		0.39	B;B;B;.;.
Vest4		0.38
MutPred		0.47		Loss of ubiquitination at K99 (P = 0.0318);Loss of ubiquitination at K99 (P = 0.0318);Loss of ubiquitination at K99 (P = 0.0318);.;.;
MVP		0.88
MPC		0.53
ClinPred		0.92	D
GERP RS		4.3
Varity_R		0.29
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-15262364;