chr12-15109322-T-G

Variant names:

• chr12-15109322-T-G
• rs1192094527
• NM_032918.3:c.388A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032918.3(RERG):​c.388A>C​(p.Thr130Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. T130A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RERG NM_032918.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.20
• 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 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.388A>C	p.Thr130Pro	missense_variant	Exon 5 of 5	ENST00000256953.6	NP_116307.1
RERG	NM_001190726.2	c.331A>C	p.Thr111Pro	missense_variant	Exon 4 of 4		NP_001177655.1
RERG	XM_047429797.1	c.379A>C	p.Thr127Pro	missense_variant	Exon 5 of 5		XP_047285753.1
RERG	XM_047429798.1	c.*242A>C		downstream_gene_variant			XP_047285754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERG	ENST00000256953.6	c.388A>C	p.Thr130Pro	missense_variant	Exon 5 of 5	1	NM_032918.3	ENSP00000256953.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D;D;D;.
Eigen	Benign	0.044
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	.;.;D;T
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.65	D;D;D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.8	L;L;L;.
PhyloP100		6.2
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.2	D;D;D;D
REVEL	Uncertain	0.55
Sift	Benign	0.047	D;D;D;D
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.019	B;B;B;.
Vest4		0.59
MutPred		0.38		Loss of phosphorylation at T130 (P = 0.104);Loss of phosphorylation at T130 (P = 0.104);Loss of phosphorylation at T130 (P = 0.104);.;
MVP		0.91
MPC		1.2
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.87
gMVP		0.83
Mutation Taster		=23/77	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

dbSNP: rs1192094527; hg19: chr12-15262256;