3-101651685-TAA-T

Variant names:

• chr3-101651685-TAA-T
• rs56200814
• NM_014415.4:c.2645-4_2645-3delTT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_014415.4(ZBTB11):​c.2645-4_2645-3delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0817 in 1,295,880 control chromosomes in the GnomAD database, including 563 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.055 (559 hom., cov: 0)
  • Exomes 𝑓: 0.085 (4 hom.)
• Consequence: ZBTB11 NM_014415.4 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.902

Genes affected

ZBTB11 (HGNC:16740): (zinc finger and BTB domain containing 11) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Located in nucleoplasm. Implicated in autosomal recessive non-syndromic intellectual disability. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 3-101651685-TAA-T is Benign according to our data. Variant chr3-101651685-TAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 3060760.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB11	NM_014415.4	c.2645-4_2645-3delTT		splice_region_variant, intron_variant	Intron 10 of 10	ENST00000312938.5	NP_055230.2
ZBTB11	XM_011512689.3	c.2450-4_2450-3delTT		splice_region_variant, intron_variant	Intron 10 of 10		XP_011510991.1
ZBTB11	XM_011512690.3	c.1793-4_1793-3delTT		splice_region_variant, intron_variant	Intron 8 of 8		XP_011510992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB11	ENST00000312938.5	c.2645-4_2645-3delTT		splice_region_variant, intron_variant	Intron 10 of 10	1	NM_014415.4	ENSP00000326200.4

Frequencies

GnomAD3 genomes AF: 0.0546 AC: 7005 AN: 128314 Hom.: 559 Cov.: 0

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0171

Gnomad ASJ AF: 0.000323

Gnomad EAS AF: 0.00111

Gnomad SAS AF: 0.00563

Gnomad FIN AF: 0.00804

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00129

Gnomad OTH AF: 0.0362

GnomAD3 exomes AF: 0.193 AC: 15046 AN: 78032 Hom.: 9 AF XY: 0.194 AC XY: 8229 AN XY: 42502

Gnomad AFR exome AF: 0.222

Gnomad AMR exome AF: 0.154

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.168

Gnomad SAS exome AF: 0.145

Gnomad FIN exome AF: 0.226

Gnomad NFE exome AF: 0.204

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.0847 AC: 98878 AN: 1167562 Hom.: 4 AF XY: 0.0862 AC XY: 48844 AN XY: 566598

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.0880

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.0778

Gnomad4 OTH exome AF: 0.0972

GnomAD4 genome AF: 0.0547 AC: 7013 AN: 128318 Hom.: 559 Cov.: 0 AF XY: 0.0530 AC XY: 3242 AN XY: 61188

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.0171

Gnomad4 ASJ AF: 0.000323

Gnomad4 EAS AF: 0.000892

Gnomad4 SAS AF: 0.00567

Gnomad4 FIN AF: 0.00804

Gnomad4 NFE AF: 0.00129

Gnomad4 OTH AF: 0.0359

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ZBTB11-related disorder Benign:1

Oct 24, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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: rs56200814; hg19: chr3-101370529;