chr6-109465671-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014797.3(ZBTB24):​c.*180T>C variant causes a 3 prime UTR 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ZBTB24
NM_014797.3 3_prime_UTR

Scores

11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.341
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06294438).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZBTB24NM_014797.3 linkuse as main transcriptc.*180T>C 3_prime_UTR_variant 7/7 ENST00000230122.4 NP_055612.2
MICAL1NM_001286613.2 linkuse as main transcriptc.7T>C p.Cys3Arg missense_variant 1/25 NP_001273542.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZBTB24ENST00000230122.4 linkuse as main transcriptc.*180T>C 3_prime_UTR_variant 7/71 NM_014797.3 ENSP00000230122 P1O43167-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 18, 2023This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 3 of the MICAL1 protein (p.Cys3Arg). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with MICAL1-related conditions. This variant is not present in population databases (gnomAD no frequency). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
1.3
DANN
Benign
0.44
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.088
N
LIST_S2
Benign
0.19
T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.063
T
MetaSVM
Benign
-0.98
T
MutationTaster
Benign
1.0
N;N
Vest4
0.066
MVP
0.24
ClinPred
0.037
T
GERP RS
-5.3
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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: chr6-109786874; API