Variant 12-18081241-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001286201.2(RERGL):c.565A>G(p.Met189Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,612,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

RERGL
NM_001286201.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17

Variant links:

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]

RERGL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042647123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RERGL	NM_001286201.2 link	c.565A>G	p.Met189Val	missense_variant	5/5	ENST00000538724.6	NP_001273130.1	Q9H628F5H686
RERGL	NM_024730.4 link	c.568A>G	p.Met190Val	missense_variant	6/6		NP_079006.1	Q9H628
RERGL	NR_104413.1 link	n.515A>G		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RERGL	ENST00000538724.6 link	c.565A>G	p.Met189Val	missense_variant	5/5	2	NM_001286201.2	ENSP00000437814.1	F5H686
RERGL	ENST00000229002.6 link	c.568A>G	p.Met190Val	missense_variant	6/6	1		ENSP00000229002.2	Q9H628
RERGL	ENST00000540148.5 link	n.574A>G		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151398

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251338

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000335

AC:

AN:

1461414

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

726964

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151398

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73812

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2024

The c.568A>G (p.M190V) 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 568, causing the methionine (M) at amino acid position 190 to be replaced by a valine (V). 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

Benign

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.00032

T;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.56

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.

PrimateAI

Benign

0.44

PROVEAN

Benign

0.73

N;N

REVEL

Benign

0.11

Sift

Benign

0.66

T;T

Sift4G

Benign

0.59

T;T

Polyphen

0.0010

B;B

Vest4

0.21

MVP

0.22

MPC

0.015

ClinPred

0.040

GERP RS

-0.30

Varity_R

0.10

gMVP

0.46

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over