11-66843465-C-G

Position:

chr11-66843465-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005133.3(RCE1):c.10C>G(p.Leu4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000354 in 1,414,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L4Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

RCE1
NM_005133.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.264

Variant links:

Genes affected

RCE1 (HGNC:13721): (Ras converting CAAX endopeptidase 1) This gene encodes an integral membrane protein which is classified as a member of the metalloproteinase family. This enzyme is thought to function in the maintenance and processing of CAAX-type prenylated proteins. [provided by RefSeq, Jul 2008]

RCE1 links:

C11orf80 (HGNC:26197): (TOP6B like initiator of meiotic double strand breaks) Predicted to be involved in meiotic DNA double-strand break formation and reciprocal meiotic recombination. Predicted to be located in chromosome. Implicated in gestational trophoblastic neoplasm. [provided by Alliance of Genome Resources, Apr 2022]

C11orf80 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.14266905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RCE1	NM_005133.3 linkuse as main transcript	c.10C>G	p.Leu4Val	missense_variant	1/8	ENST00000309657.8	NP_005124.1
C11orf80	NM_001302084.2 linkuse as main transcript	c.*231C>G		3_prime_UTR_variant	15/15	ENST00000540737.7	NP_001289013.1
RCE1	NM_001032279.2 linkuse as main transcript	c.-299C>G		5_prime_UTR_variant	1/8		NP_001027450.1
C11orf80	NM_024650.3 linkuse as main transcript	c.*231C>G		3_prime_UTR_variant	17/17		NP_078926.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCE1	ENST00000309657.8 linkuse as main transcript	c.10C>G	p.Leu4Val	missense_variant	1/8	1	NM_005133.3	ENSP00000309163	P1
C11orf80	ENST00000540737.7 linkuse as main transcript	c.*231C>G		3_prime_UTR_variant	15/15	2	NM_001302084.2	ENSP00000444319	A2

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000371

AC:

AN:

26926

Hom.:

AF XY:

0.0000610

AC XY:

AN XY:

16394

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000788

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000349

AC:

AN:

1262218

Hom.:

Cov.:

AF XY:

0.0000307

AC XY:

AN XY:

619730

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:

0.0000417

Gnomad4 OTH exome

AF:

0.0000192

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152016

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000340

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 22, 2024

The c.10C>G (p.L4V) alteration is located in exon 1 (coding exon 1) of the RCE1 gene. This alteration results from a C to G substitution at nucleotide position 10, causing the leucine (L) at amino acid position 4 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

0.089

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.065

T;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.77

T;T

M_CAP

Pathogenic

0.62

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.38

N;N

REVEL

Benign

0.063

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.56

P;.

Vest4

0.13

MutPred

0.20

Gain of catalytic residue at L4 (P = 0.0506);Gain of catalytic residue at L4 (P = 0.0506);

MVP

0.043

MPC

0.51

ClinPred

0.23

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.23

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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