ENST00000525449.6:c.-210A>G

Variant names:

• chr11-66748457-A-G
• rs1943051731
• ENST00000525449.6:c.-210A>G

Variant summary

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

The ENST00000525449.6(TOP6BL):​c.-210A>G variant causes a 5 prime UTR 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TOP6BL ENST00000525449.6 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.75
• Publications: 0 publications found

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]

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=0.2232596).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000525449.6. 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
	TOP6BL	NM_001302084.2	MANE Select	c.-30+3538A>G		intron	N/A	NP_001289013.1	Q8N6T0-6
	TOP6BL	NM_024650.4		c.109A>G	p.Ile37Val	missense	Exon 2 of 17	NP_078926.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOP6BL	ENST00000525449.6	TSL:1	c.-210A>G		5_prime_UTR	Exon 1 of 15	ENSP00000434648.2	A0A140TA08
	TOP6BL	ENST00000540737.7	TSL:2 MANE Select	c.-30+3538A>G		intron	N/A	ENSP00000444319.1	Q8N6T0-6
	TOP6BL	ENST00000525908.6	TSL:2	c.109A>G	p.Ile37Val	missense	Exon 2 of 17	ENSP00000432039.3	A0A2U3TZP7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	1.0
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.7
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.062
Sift	Pathogenic	0.0	D
MVP		0.12
MPC		0.065
ClinPred		0.58	D
GERP RS		6.1
PromoterAI		-0.0015	Neutral
gMVP		0.015
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs1943051731; hg19: chr11-66515928;