12-18081247-T-C

Position:

• chr12-18081247-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001286201.2(RERGL):​c.559A>G​(p.Lys187Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RERGL NM_001286201.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.09

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27960235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RERGL	NM_001286201.2	c.559A>G	p.Lys187Glu	missense_variant	5/5	ENST00000538724.6
RERGL	NM_024730.4	c.562A>G	p.Lys188Glu	missense_variant	6/6
RERGL	NR_104413.1	n.509A>G		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RERGL	ENST00000538724.6	c.559A>G	p.Lys187Glu	missense_variant	5/5	2	NM_001286201.2	P1
RERGL	ENST00000229002.6	c.562A>G	p.Lys188Glu	missense_variant	6/6	1
RERGL	ENST00000540148.5	n.568A>G		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2023

The c.562A>G (p.K188E) alteration is located in exon 6 (coding exon 5) of the RERGL gene. This alteration results from a A to G substitution at nucleotide position 562, causing the lysine (K) at amino acid position 188 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0071	T;.
Eigen	Benign	0.097
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	0.92	D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.8	N;N
REVEL	Uncertain	0.44
Sift	Uncertain	0.016	D;D
Sift4G	Uncertain	0.020	D;D
Polyphen		0.68	P;P
Vest4		0.47
MutPred		0.31		Loss of MoRF binding (P = 0.0079);.;
MVP		0.43
MPC		0.038
ClinPred		0.95	D
GERP RS		3.4
Varity_R		0.26
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-18234181;