11-66756337-CTTT-CT

Variant names:

• chr11-66756337-CTT-C
• rs538618909
• NM_001302084.2:c.-29-2697_-29-2696delTT

Variant summary

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

The NM_024650.4(TOP6BL):​c.170-7_170-6delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 939,494 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000026 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TOP6BL NM_024650.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.750

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOP6BL	NM_001302084.2	c.-29-2697_-29-2696delTT		intron_variant	Intron 1 of 14	ENST00000540737.7	NP_001289013.1
TOP6BL	NM_024650.4	c.170-7_170-6delTT		splice_region_variant, intron_variant	Intron 2 of 16		NP_078926.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C11orf80	ENST00000540737.7	c.-29-2705_-29-2704delTT		intron_variant	Intron 1 of 14	2	NM_001302084.2	ENSP00000444319.1
C11orf80	ENST00000525449.6	c.-149-15_-149-14delTT		intron_variant	Intron 1 of 14	1		ENSP00000434648.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149140 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000315 AC: 8 AN: 25382 Hom.: 0 AF XY: 0.000504 AC XY: 7 AN XY: 13902

Gnomad AFR exome AF: 0.000883

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.000547

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000507

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000308

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000255 AC: 24 AN: 939494 Hom.: 0 AF XY: 0.0000418 AC XY: 19 AN XY: 454532

Gnomad4 AFR exome AF: 0.0000546

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000887

Gnomad4 EAS exome AF: 0.000133

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000190

Gnomad4 OTH exome AF: 0.0000298

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 149140 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 72638

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000241 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs538618909; hg19: chr11-66523808;