chr11-66843966-C-T

Variant names:

• chr11-66843966-C-T
• rs1945150138
• NM_005133.3:c.299C>T

Variant summary

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

The NM_005133.3(RCE1):​c.299C>T​(p.Ser100Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. S100C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RCE1 NM_005133.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.12
• 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]

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCE1	NM_005133.3	MANE Select	c.299C>T	p.Ser100Phe	missense	Exon 3 of 8	NP_005124.1	Q9Y256
	RCE1	NM_001032279.2		c.-14C>T		5_prime_UTR	Exon 3 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.299C>T	p.Ser100Phe	missense	Exon 3 of 8	ENSP00000309163.3	Q9Y256
	RCE1	ENST00000524849.5	TSL:1	n.295C>T		non_coding_transcript_exon	Exon 3 of 8	ENSP00000436300.1	E9PPV9
	RCE1	ENST00000524506.5	TSL:5	c.299C>T	p.Ser100Phe	missense	Exon 3 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	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0041	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.10
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.022	D
Polyphen		0.91	P
Vest4		0.71
MutPred		0.43		Loss of disorder (P = 0.0912)
MVP		0.13
MPC		1.2
ClinPred		0.96	D
GERP RS		4.3
PromoterAI		0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.66
Mutation Taster		=59/41	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

Other links and lift over

dbSNP: rs1945150138; hg19: chr11-66611437;