Genetic Variant ZBTB24:p.Gly693Val (chr6-109465867-C-A) – 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_014797.3(ZBTB24):c.2078G>T(p.Gly693Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G693D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ZBTB24
NM_014797.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.407

Publications

1 publications found

Variant links:

Genes affected

ZBTB24 (HGNC:21143): (zinc finger and BTB domain containing 24) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be located in nucleus. Implicated in immunodeficiency-centromeric instability-facial anomalies syndrome 2. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB24 links:

MICAL1 (HGNC:20619): (microtubule associated monooxygenase, calponin and LIM domain containing 1) This gene encodes an enzyme that oxidizes methionine residues on actin, thereby promoting depolymerization of actin filaments. This protein interacts with and regulates signalling by NEDD9/CAS-L (neural precursor cell expressed, developmentally down-regulated 9). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

MICAL1 Gene-Disease associations (from GenCC):

epilepsy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

MICAL1 links:

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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=0.053503662).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014797.3. 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
	ZBTB24	NM_014797.3	MANE Select	c.2078G>T	p.Gly693Val	missense	Exon 7 of 7	NP_055612.2	O43167-1
	MICAL1	NM_001286613.2		c.-190G>T		5_prime_UTR	Exon 1 of 25	NP_001273542.1	Q8TDZ2-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBTB24	ENST00000230122.4	TSL:1 MANE Select	c.2078G>T	p.Gly693Val	missense	Exon 7 of 7	ENSP00000230122.4	O43167-1
ZBTB24	ENST00000698516.1		c.2078G>T	p.Gly693Val	missense	Exon 7 of 7	ENSP00000513766.1	O43167-1
ZBTB24	ENST00000698513.1		c.1910G>T	p.Gly637Val	missense	Exon 6 of 6	ENSP00000513763.1	A0A8V8TLS8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0072

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.51

M_CAP

Benign

0.010

MetaRNN

Benign

0.054

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.69

PhyloP100

0.41

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.54

REVEL

Benign

0.11

Sift

Benign

0.031

Sift4G

Uncertain

0.014

Polyphen

0.0

Vest4

0.056

MutPred

0.12

Loss of loop (P = 0.0389)

MVP

0.23

MPC

0.74

ClinPred

0.44

GERP RS

1.4

PromoterAI

-0.067

Neutral

(source)

Varity_R

0.039

gMVP

0.079

Mutation Taster

=94/6

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

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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