12-15121072-G-T

Variant names:

• chr12-15121072-G-T
• rs374626892
• NM_032918.3:c.109C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_032918.3(RERG):​c.109C>A​(p.Pro37Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. P37S) 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: 5.92
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.924

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RERG	NM_032918.3	c.109C>A	p.Pro37Thr	missense_variant	Exon 3 of 5	ENST00000256953.6	NP_116307.1
RERG	XM_047429797.1	c.100C>A	p.Pro34Thr	missense_variant	Exon 3 of 5		XP_047285753.1
RERG	XM_047429798.1	c.109C>A	p.Pro37Thr	missense_variant	Exon 3 of 6		XP_047285754.1
RERG	NM_001190726.2	c.62-9655C>A		intron_variant	Intron 2 of 3		NP_001177655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERG	ENST00000256953.6	c.109C>A	p.Pro37Thr	missense_variant	Exon 3 of 5	1	NM_032918.3	ENSP00000256953.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.62	D;D;D;.;.;D
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	.;.;D;D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.92	D;D;D;D;D;D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Benign	1.9	L;L;L;.;.;.
PhyloP100		5.9
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-6.7	D;D;D;D;D;D
REVEL	Pathogenic	0.80
Sift	Uncertain	0.013	D;D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;.;D;.
Polyphen		1.0	D;D;D;.;.;.
Vest4		0.71
MutPred		0.81		Gain of catalytic residue at P37 (P = 0.0488);Gain of catalytic residue at P37 (P = 0.0488);Gain of catalytic residue at P37 (P = 0.0488);.;Gain of catalytic residue at P37 (P = 0.0488);Gain of catalytic residue at P37 (P = 0.0488);
MVP		0.94
MPC		1.1
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.74
gMVP		0.77
Mutation Taster		=68/32	polymorphism

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: rs374626892; hg19: chr12-15274006;