chr12-18088908-G-C

Variant names:

• chr12-18088908-G-C
• rs1947244063
• NM_001286201.2:c.101C>G

Variant summary

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

The NM_001286201.2(RERGL):​c.101C>G​(p.Ser34Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,152 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S34F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RERGL NM_001286201.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.22
• Publications: 0 publications found

Genes affected

RERGL (HGNC:26213): (RERG like) Predicted to enable G protein activity and GTP binding activity. [provided by Alliance of Genome Resources, Apr 2022]

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, 0.859

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286201.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RERGL	NM_001286201.2	MANE Select	c.101C>G	p.Ser34Cys	missense	Exon 2 of 5	NP_001273130.1	F5H686
	RERGL	NM_024730.4		c.104C>G	p.Ser35Cys	missense	Exon 3 of 6	NP_079006.1	Q9H628
	RERGL	NR_104413.1		n.154C>G		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RERGL	ENST00000538724.6	TSL:2 MANE Select	c.101C>G	p.Ser34Cys	missense	Exon 2 of 5	ENSP00000437814.1	F5H686
	RERGL	ENST00000229002.6	TSL:1	c.104C>G	p.Ser35Cys	missense	Exon 3 of 6	ENSP00000229002.2	Q9H628
	RERGL	ENST00000536890.1	TSL:3	c.101C>G	p.Ser34Cys	missense	Exon 2 of 5	ENSP00000437490.1	G5EA41

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452152 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 723126

African (AFR) AF: 0.00 AC: 0 AN: 33190

American (AMR) AF: 0.00 AC: 0 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26026

East Asian (EAS) AF: 0.00 AC: 0 AN: 39508

South Asian (SAS) AF: 0.00 AC: 0 AN: 86014

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103648

Other (OTH) AF: 0.00 AC: 0 AN: 60036

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	0.47	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.2
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.6	D
REVEL	Pathogenic	0.79
Sift	Benign	0.047	D
Sift4G	Uncertain	0.040	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.62		Gain of catalytic residue at S39 (P = 0.034)
MVP		0.53
MPC		0.12
ClinPred		0.98	D
GERP RS		4.2
Varity_R		0.26
gMVP		0.55
Mutation Taster		=33/67	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1947244063; hg19: chr12-18241842;