RCE1 p.Val39Leu

Variant names:

• chr11-66843570-G-T
• NM_005133.3:c.115G>T
• RCE1 p.Val39Leu

Your query was ambiguous. Multiple possible variants found:

• chr11-66843570-G-T
• chr11-66843570-G-C
• chr11-66843570-GTG-TTA
• chr11-66843570-GTG-CTT
• chr11-66843570-GTG-CTC
• chr11-66843570-GTG-CTA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005133.3(RCE1):​c.115G>T​(p.Val39Leu) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RCE1 NM_005133.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.90
• Publications: 0 publications found

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]

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19713265).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCE1	NM_005133.3	MANE Select	c.115G>T	p.Val39Leu	missense	Exon 1 of 8	NP_005124.1	Q9Y256
	RCE1	NM_001032279.2		c.-194G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001027450.1
	RCE1	NM_001032279.2		c.-194G>T		5_prime_UTR	Exon 1 of 8	NP_001027450.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCE1	ENST00000309657.8	TSL:1 MANE Select	c.115G>T	p.Val39Leu	missense	Exon 1 of 8	ENSP00000309163.3	Q9Y256
	RCE1	ENST00000524849.5	TSL:1	n.115G>T		non_coding_transcript_exon	Exon 1 of 8	ENSP00000436300.1	E9PPV9
	RCE1	ENST00000524506.5	TSL:5	c.115G>T	p.Val39Leu	missense	Exon 1 of 7	ENSP00000436600.1	E9PI08

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.41	N
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.9
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.11
Sift	Benign	0.19	T
Sift4G	Benign	0.11	T
PromoterAI		0.022	Neutral
Varity_R		0.21
gMVP		0.38
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-66611041;