11-66842947-G-C

Variant names:

• chr11-66842947-G-C
• NM_001302084.2:c.1348G>C

Variant summary

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

The NM_001302084.2(TOP6BL):​c.1348G>C​(p.Glu450Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,403,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 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: 7.1e-7 (0 hom.)
• Consequence: TOP6BL NM_001302084.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.767

Genes affected

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]

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

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=0.07599324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOP6BL	NM_001302084.2	c.1348G>C	p.Glu450Gln	missense_variant	Exon 14 of 15	ENST00000540737.7	NP_001289013.1
TOP6BL	NM_024650.4	c.1699G>C	p.Glu567Gln	missense_variant	Exon 16 of 17		NP_078926.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C11orf80	ENST00000540737.7	c.1348G>C	p.Glu450Gln	missense_variant	Exon 14 of 15	2	NM_001302084.2	ENSP00000444319.1
C11orf80	ENST00000525449.6	c.1270G>C	p.Glu424Gln	missense_variant	Exon 14 of 15	1		ENSP00000434648.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1403826 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 693122

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: 9.23e-7

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	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Uncertain	0.99
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.63	T;T;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.076	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-0.62	.;N;N;N;.;.;.
REVEL	Benign	0.022
Sift	Benign	0.057	.;T;T;T;.;.;.
Sift4G	Uncertain	0.017	.;.;D;D;.;D;D
Polyphen		0.10	.;.;B;B;.;.;.
Vest4		0.19, 0.22, 0.19, 0.20
MVP		0.055
MPC		0.33
ClinPred		0.13	T
GERP RS		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.12

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: chr11-66610418;