11-66756337-CTTT-CTTTTTT

Variant names:

• chr11-66756337-C-CTTT
• NM_001302084.2:c.-29-2698_-29-2696dupTTT

Variant summary

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

The NM_024650.4(TOP6BL):​c.170-8_170-6dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000851 in 939,818 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000085 (0 hom.)
• Consequence: TOP6BL NM_024650.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538

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.-29-2698_-29-2696dupTTT		intron_variant	Intron 1 of 14	ENST00000540737.7	NP_001289013.1
TOP6BL	NM_024650.4	c.170-8_170-6dupTTT		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.-29-2706_-29-2705insTTT		intron_variant	Intron 1 of 14	2	NM_001302084.2	ENSP00000444319.1
C11orf80	ENST00000525449.6	c.-149-16_-149-15insTTT		intron_variant	Intron 1 of 14	1		ENSP00000434648.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000851 AC: 8 AN: 939818 Hom.: 0 Cov.: 24 AF XY: 0.00000880 AC XY: 4 AN XY: 454742

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: 0.0000556

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000634

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr11-66523808;