Genetic Variant ZBTB11:p.His94Gln (chr3-101676633-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014415.4(ZBTB11):c.282C>G(p.His94Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H94Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

ZBTB11
NM_014415.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.287

Publications

0 publications found

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:

LOC124906262 (HGNC:):

LOC124906262 links:

ZBTB11-AS1 (HGNC:48573): (ZBTB11 antisense RNA 1)

ZBTB11-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06518784).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014415.4. 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
	ZBTB11	NM_014415.4	MANE Select	c.282C>G	p.His94Gln	missense	Exon 1 of 11	NP_055230.2	O95625
	ZBTB11-AS1	NR_024407.1		n.204G>C		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBTB11	ENST00000312938.5	TSL:1 MANE Select	c.282C>G	p.His94Gln	missense	Exon 1 of 11	ENSP00000326200.4	O95625
ZBTB11	ENST00000461821.1	TSL:1	c.282C>G	p.His94Gln	missense	Exon 1 of 2	ENSP00000417369.1	C9J2L2
ZBTB11	ENST00000704111.1		c.282C>G	p.His94Gln	missense	Exon 1 of 10	ENSP00000515702.1	A0A994J7A5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.17e-7

AC:

AN:

1394104

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

686164

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31256

American (AMR)

AF:

0.00

AC:

AN:

35460

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22028

East Asian (EAS)

AF:

0.00

AC:

AN:

38534

South Asian (SAS)

AF:

0.00

AC:

AN:

77652

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50222

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5474

European-Non Finnish (NFE)

AF:

9.29e-7

AC:

AN:

1076208

Other (OTH)

AF:

0.00

AC:

AN:

57270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.039

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.57

M_CAP

Benign

0.039

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

0.29

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.74

REVEL

Benign

0.024

Sift

Benign

0.21

Sift4G

Benign

0.40

Polyphen

0.0030

Vest4

0.20

MutPred

0.24

Gain of helix (P = 0.0325)

MVP

0.24

MPC

1.1

ClinPred

0.16

GERP RS

-1.8

PromoterAI

-0.036

Neutral

(source)

Varity_R

0.089

gMVP

0.37

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over