rs80276325

Variant names:

• chr11-66788262-T-A
• rs80276325
• NM_001302084.2:c.128T>A

Your query was ambiguous. Multiple possible variants found:

• chr11-66788262-T-A
• chr11-66788262-T-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.128T>A​(p.Ile43Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: TOP6BL NM_001302084.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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]

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=0.075289965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOP6BL	NM_001302084.2	c.128T>A	p.Ile43Asn	missense_variant	Exon 3 of 15	ENST00000540737.7	NP_001289013.1
TOP6BL	NM_024650.4	c.479T>A	p.Ile160Asn	missense_variant	Exon 5 of 17		NP_078926.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C11orf80	ENST00000540737.7	c.128T>A	p.Ile43Asn	missense_variant	Exon 3 of 15	2	NM_001302084.2	ENSP00000444319.1
C11orf80	ENST00000525449.6	c.161T>A	p.Ile54Asn	missense_variant	Exon 4 of 15	1		ENSP00000434648.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	5.2
DANN	Benign	0.96
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.71	T;T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.075	T;T;T;T;T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-1.5	N;N;D;.;D
REVEL	Benign	0.095
Sift	Benign	0.16	T;T;D;.;D
Sift4G	Uncertain	0.025	.;.;D;.;D
Vest4		0.56, 0.55
MVP		0.12
MPC		0.12
ClinPred		0.25	T
GERP RS		-5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.15

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

LitVar

Other links and lift over

dbSNP: rs80276325; hg19: chr11-66555733;