rs193920908

chr12-18081394-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RERGL	NM_001286201.2	c.412C>A	p.Gln138Lys	missense_variant	5/5	ENST00000538724.6
RERGL	NM_024730.4	c.415C>A	p.Gln139Lys	missense_variant	6/6
RERGL	NR_104413.1	n.362C>A		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RERGL	ENST00000538724.6	c.412C>A	p.Gln138Lys	missense_variant	5/5	2	NM_001286201.2	P1

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

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.2	L;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.80	N;N
REVEL	Benign	0.17
Sift	Benign	0.058	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.20	B;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

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: rs193920908; hg19: chr12-18234328; COSMIC: COSV57462929;