Genetic Variant ZBTB11:c.*10_*13delTGAA (chr3-101651152-CTTCA-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_014415.4(ZBTB11):c.*10_*13delTGAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,547,052 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 2 hom. )

Consequence

ZBTB11
NM_014415.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.691

Variant links:

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]

ZBTB11 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 3-101651152-CTTCA-C is Benign according to our data. Variant chr3-101651152-CTTCA-C is described in ClinVar as [Likely_benign]. Clinvar id is 3043173.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000145 (22/152242) while in subpopulation SAS AF= 0.00145 (7/4822). AF 95% confidence interval is 0.00068. There are 0 homozygotes in gnomad4. There are 15 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ZBTB11	NM_014415.4 link	c.10_13delTGAA	3_prime_UTR_variant	Exon 11 of 11	ENST00000312938.5	NP_055230.2	O95625Q59H97
ZBTB11	XM_011512689.3 link	c.10_13delTGAA	3_prime_UTR_variant	Exon 11 of 11		XP_011510991.1
ZBTB11	XM_011512690.3 link	c.10_13delTGAA	3_prime_UTR_variant	Exon 9 of 9		XP_011510992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB11	ENST00000312938 link	c.10_13delTGAA		3_prime_UTR_variant	Exon 11 of 11	1	NM_014415.4	ENSP00000326200.4		O95625

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000227

AC:

AN:

198272

Hom.:

AF XY:

0.000257

AC XY:

AN XY:

105168

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000240

Gnomad ASJ exome

AF:

0.000185

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000180

Gnomad OTH exome

AF:

0.000215

GnomAD4 exome

AF:

0.000185

AC:

258

AN:

1394810

Hom.:

AF XY:

0.000212

AC XY:

146

AN XY:

687724

show subpopulations

Gnomad4 AFR exome

AF:

0.0000321

Gnomad4 AMR exome

AF:

0.000235

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00150

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000108

Gnomad4 OTH exome

AF:

0.000243

GnomAD4 genome

AF:

0.000145

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ZBTB11-related disorder

Benign:1

Jun 21, 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

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over