NM_014797.3:c.2094A>G

Variant names:

• chr6-109465851-T-C
• rs1554227574
• NM_014797.3:c.2094A>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_014797.3(ZBTB24):​c.2094A>G​(p.Ter698Trpext*?) variant causes a stop lost change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZBTB24 NM_014797.3 stop_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.18
• Publications: 0 publications found

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]

MICAL1 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_014797.3 Downstream stopcodon found after 44 codons.

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.2094A>G	p.Ter698Trpext*?	stop_lost	Exon 7 of 7	NP_055612.2	O43167-1
	MICAL1	NM_001286613.2		c.-174A>G		5_prime_UTR	Exon 1 of 25	NP_001273542.1	Q8TDZ2-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB24	ENST00000230122.4	TSL:1 MANE Select	c.2094A>G	p.Ter698Trpext*?	stop_lost	Exon 7 of 7	ENSP00000230122.4	O43167-1
	ZBTB24	ENST00000698516.1		c.2094A>G	p.Ter698Trpext*?	stop_lost	Exon 7 of 7	ENSP00000513766.1	O43167-1
	ZBTB24	ENST00000698513.1		c.1926A>G	p.Ter642Trpext*?	stop_lost	Exon 6 of 6	ENSP00000513763.1	A0A8V8TLS8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Immunodeficiency-centromeric instability-facial anomalies syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	18
DANN	Benign	0.89
Eigen	Pathogenic	0.99
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		4.2
Vest4		0.0070
GERP RS		4.2
PromoterAI		0.099	Neutral
Mutation Taster		=46/154	disease causing

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

Other links and lift over

dbSNP: rs1554227574; hg19: chr6-109787054;