rs193920908

Variant names:

• chr12-18081394-G-T
• rs193920908
• NM_001286201.2:c.412C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001286201.2(RERGL):​c.412C>A​(p.Gln138Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RERGL NM_001286201.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.76
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21999922).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RERGL	NM_001286201.2	MANE Select	c.412C>A	p.Gln138Lys	missense	Exon 5 of 5	NP_001273130.1
	RERGL	NM_024730.4		c.415C>A	p.Gln139Lys	missense	Exon 6 of 6	NP_079006.1
	RERGL	NR_104413.1		n.362C>A		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RERGL	ENST00000538724.6	TSL:2 MANE Select	c.412C>A	p.Gln138Lys	missense	Exon 5 of 5	ENSP00000437814.1
	RERGL	ENST00000229002.6	TSL:1	c.415C>A	p.Gln139Lys	missense	Exon 6 of 6	ENSP00000229002.2
	RERGL	ENST00000540148.5	TSL:3	n.421C>A		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer Uncertain:1

Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Uncertain	0.97
DEOGEN2	Benign	0.097	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.0081
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.2	L
PhyloP100		6.8
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.17
Sift	Benign	0.058	T
Sift4G	Benign	0.18	T
Polyphen		0.20	B
Vest4		0.35
MutPred		0.48		Gain of ubiquitination at Q139 (P = 0.0192)
MVP		0.33
MPC		0.017
ClinPred		0.68	D
GERP RS		3.8
Varity_R		0.36
gMVP		0.53
Mutation Taster		=61/39	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: rs193920908; hg19: chr12-18234328; COSMIC: COSV57462929;