NM_032918.3:c.253G>C

Variant names:

• chr12-15109457-C-G
• rs777057953
• NM_032918.3:c.253G>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_032918.3(RERG):​c.253G>C​(p.Asp85His) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.944

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RERG	NM_032918.3	c.253G>C	p.Asp85His	missense_variant	Exon 5 of 5	ENST00000256953.6	NP_116307.1
RERG	NM_001190726.2	c.196G>C	p.Asp66His	missense_variant	Exon 4 of 4		NP_001177655.1
RERG	XM_047429797.1	c.244G>C	p.Asp82His	missense_variant	Exon 5 of 5		XP_047285753.1
RERG	XM_047429798.1	c.*107G>C		downstream_gene_variant			XP_047285754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERG	ENST00000256953.6	c.253G>C	p.Asp85His	missense_variant	Exon 5 of 5	1	NM_032918.3	ENSP00000256953.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251268 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135790

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: 0.0000981

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461700 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727138

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: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.40
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	D;D;D;.;.
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	.;.;D;D;D
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.94	D;D;D;D;D
MetaSVM	Uncertain	0.76	D
MutationAssessor	Pathogenic	3.5	H;H;H;.;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.9	N;N;N;N;N
REVEL	Pathogenic	0.85
Sift	Uncertain	0.0040	D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;.
Polyphen		1.0	D;D;D;.;.
Vest4		0.91
MutPred		0.86		Loss of stability (P = 0.0593);Loss of stability (P = 0.0593);Loss of stability (P = 0.0593);.;.;
MVP		0.95
MPC		1.1
ClinPred		0.92	D
GERP RS		4.3
Varity_R		0.69
gMVP		0.85

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

Other links and lift over

dbSNP: rs777057953; hg19: chr12-15262391;