NM_001286201.2:c.101C>T

Variant names:

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

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>T​(p.Ser34Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S34S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RERGL NM_001286201.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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, 0.882

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>T	p.Ser34Phe	missense	Exon 2 of 5	NP_001273130.1	F5H686
	RERGL	NM_024730.4		c.104C>T	p.Ser35Phe	missense	Exon 3 of 6	NP_079006.1	Q9H628
	RERGL	NR_104413.1		n.154C>T		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>T	p.Ser34Phe	missense	Exon 2 of 5	ENSP00000437814.1	F5H686
	RERGL	ENST00000229002.6	TSL:1	c.104C>T	p.Ser35Phe	missense	Exon 3 of 6	ENSP00000229002.2	Q9H628
	RERGL	ENST00000536890.1	TSL:3	c.101C>T	p.Ser34Phe	missense	Exon 2 of 5	ENSP00000437490.1	G5EA41

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.32	D
MutationAssessor	Pathogenic	3.3	M
PhyloP100		7.2
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.6	D
REVEL	Pathogenic	0.81
Sift	Benign	0.041	D
Sift4G	Uncertain	0.044	D
Polyphen		0.94	P
Vest4		0.85
MutPred		0.64		Loss of relative solvent accessibility (P = 0.0981)
MVP		0.55
MPC		0.10
ClinPred		0.98	D
GERP RS		4.2
Varity_R		0.39
gMVP		0.62
Mutation Taster		=32/68	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;