dbSNP rs774470995: RERGL:p.Val160Leu (chr12-18081328-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001286201.2(RERGL):c.478G>T(p.Val160Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V160M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RERGL
NM_001286201.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.61

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RERGL	NM_001286201.2 link	c.478G>T	p.Val160Leu	missense_variant	Exon 5 of 5	ENST00000538724.6	NP_001273130.1	Q9H628F5H686
RERGL	NM_024730.4 link	c.481G>T	p.Val161Leu	missense_variant	Exon 6 of 6		NP_079006.1	Q9H628
RERGL	NR_104413.1 link	n.428G>T		non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RERGL	ENST00000538724.6 link	c.478G>T	p.Val160Leu	missense_variant	Exon 5 of 5	2	NM_001286201.2	ENSP00000437814.1		F5H686

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Uncertain

0.015

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

T;.

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.78

T;T

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.70

D;D

MetaSVM

Uncertain

0.42

MutationAssessor

Pathogenic

2.9

M;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.1

N;N

REVEL

Uncertain

0.54

Sift

Uncertain

0.0070

D;D

Sift4G

Benign

0.12

T;D

Polyphen

0.44

B;B

Vest4

0.43

MutPred

0.79

Gain of disorder (P = 0.1202);.;

MVP

0.37

MPC

0.023

ClinPred

0.95

GERP RS

4.3

Varity_R

0.33

gMVP

0.72

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over