11-66843474-G-C

Variant names:

• chr11-66843474-G-C
• NM_005133.3:c.19G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005133.3(RCE1):​c.19G>C​(p.Asp7His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000774 in 1,291,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign 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: 7.7e-7 (0 hom.)
• Consequence: RCE1 NM_005133.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00

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]

ACMG classification

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=0.14152887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCE1	NM_005133.3	c.19G>C	p.Asp7His	missense_variant	Exon 1 of 8	ENST00000309657.8	NP_005124.1
TOP6BL	NM_001302084.2	c.*240G>C		3_prime_UTR_variant	Exon 15 of 15	ENST00000540737.7	NP_001289013.1
RCE1	NM_001032279.2	c.-290G>C		5_prime_UTR_variant	Exon 1 of 8		NP_001027450.1
TOP6BL	NM_024650.4	c.*240G>C		3_prime_UTR_variant	Exon 17 of 17		NP_078926.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCE1	ENST00000309657.8	c.19G>C	p.Asp7His	missense_variant	Exon 1 of 8	1	NM_005133.3	ENSP00000309163.3
C11orf80	ENST00000540737.7	c.*240G>C		3_prime_UTR_variant	Exon 15 of 15	2	NM_001302084.2	ENSP00000444319.1
C11orf80	ENST00000525449.6	c.*240G>C		downstream_gene_variant		1		ENSP00000434648.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.74e-7 AC: 1 AN: 1291476 Hom.: 0 Cov.: 32 AF XY: 0.00000157 AC XY: 1 AN XY: 635978

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: 0.0000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.064	T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.089
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.80	T;T
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.60	N;N
REVEL	Benign	0.017
Sift	Uncertain	0.015	D;D
Sift4G	Benign	0.16	T;T
Polyphen		0.12	B;.
Vest4		0.24
MutPred		0.24		Gain of MoRF binding (P = 0.025);Gain of MoRF binding (P = 0.025);
MVP		0.068
MPC		0.63
ClinPred		0.14	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.19
gMVP		0.57

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.

Other links and lift over

hg19: chr11-66610945;