Genetic Variant RCE1:p.Glu22* (chr11-66843519-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005133.3(RCE1):c.64G>T(p.Glu22*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RCE1
NM_005133.3 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.73

Publications

0 publications found

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:

TOP6BL (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]

TOP6BL Gene-Disease associations (from GenCC):

hydatidiform mole, recurrent, 4
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

TOP6BL links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005133.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RCE1	NM_005133.3	MANE Select	c.64G>T	p.Glu22*	stop_gained	Exon 1 of 8	NP_005124.1	Q9Y256
RCE1	NM_001032279.2		c.-245G>T		5_prime_UTR	Exon 1 of 8	NP_001027450.1
TOP6BL	NM_001302084.2	MANE Select	c.*285G>T		downstream_gene	N/A	NP_001289013.1	Q8N6T0-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RCE1	ENST00000309657.8	TSL:1 MANE Select	c.64G>T	p.Glu22*	stop_gained	Exon 1 of 8	ENSP00000309163.3	Q9Y256
RCE1	ENST00000524849.5	TSL:1	n.64G>T		non_coding_transcript_exon	Exon 1 of 8	ENSP00000436300.1	E9PPV9
RCE1	ENST00000524506.5	TSL:5	c.64G>T	p.Glu22*	stop_gained	Exon 1 of 7	ENSP00000436600.1	E9PI08

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1348756

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

666244

African (AFR)

AF:

0.00

AC:

AN:

27258

American (AMR)

AF:

0.00

AC:

AN:

28956

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23732

East Asian (EAS)

AF:

0.00

AC:

AN:

31980

South Asian (SAS)

AF:

0.00

AC:

AN:

75980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4364

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1067090

Other (OTH)

AF:

0.00

AC:

AN:

55994

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.55

BayesDel_noAF

Pathogenic

0.56

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Pathogenic

0.78

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Benign

0.11

PhyloP100

3.7

Vest4

0.73

GERP RS

4.5

PromoterAI

0.087

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=63/137

disease causing (fs/PTC)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over