NM_014797.3:c.860A>T

Variant names:

• chr6-109481167-T-A
• rs1456427014
• NM_014797.3:c.860A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014797.3(ZBTB24):​c.860A>T​(p.Lys287Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. K287R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZBTB24 NM_014797.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.99
• 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]

ZBTB24 Gene-Disease associations (from GenCC):

• immunodeficiency-centromeric instability-facial anomalies syndrome 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• immunodeficiency-centromeric instability-facial anomalies syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB24	NM_014797.3	MANE Select	c.860A>T	p.Lys287Met	missense	Exon 2 of 7	NP_055612.2
	ZBTB24	NM_001164313.2		c.860A>T	p.Lys287Met	missense	Exon 2 of 2	NP_001157785.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB24	ENST00000230122.4	TSL:1 MANE Select	c.860A>T	p.Lys287Met	missense	Exon 2 of 7	ENSP00000230122.4
	ZBTB24	ENST00000698516.1		c.860A>T	p.Lys287Met	missense	Exon 2 of 7	ENSP00000513766.1
	ZBTB24	ENST00000698513.1		c.860A>T	p.Lys287Met	missense	Exon 2 of 6	ENSP00000513763.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Benign	0.015
Eigen_PC	Benign	-0.061
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		3.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.12
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.073	T
Polyphen		0.99	D
Vest4		0.59
MutPred		0.38		Loss of catalytic residue at K287 (P = 9e-04)
MVP		0.31
MPC		0.62
ClinPred		0.77	D
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.085
gMVP		0.37
Mutation Taster		=79/21	polymorphism

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: rs1456427014; hg19: chr6-109802370;