chr6-109466348-C-T

Variant names:

• chr6-109466348-C-T
• rs779741867
• NM_014797.3:c.1597G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014797.3(ZBTB24):​c.1597G>A​(p.Val533Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V533L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZBTB24 NM_014797.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.104655385).

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.1597G>A	p.Val533Ile	missense	Exon 7 of 7	NP_055612.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB24	ENST00000230122.4	TSL:1 MANE Select	c.1597G>A	p.Val533Ile	missense	Exon 7 of 7	ENSP00000230122.4
	ZBTB24	ENST00000698516.1		c.1597G>A	p.Val533Ile	missense	Exon 7 of 7	ENSP00000513766.1
	ZBTB24	ENST00000698513.1		c.1429G>A	p.Val477Ile	missense	Exon 6 of 6	ENSP00000513763.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.093
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.81	L
PhyloP100		2.3
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.065
Sift	Benign	0.28	T
Sift4G	Benign	0.15	T
Polyphen		0.036	B
Vest4		0.13
MutPred		0.46		Loss of phosphorylation at T530 (P = 0.1031)
MVP		0.14
MPC		0.13
ClinPred		0.29	T
GERP RS		6.1
PromoterAI		-0.014	Neutral
Varity_R		0.035
gMVP		0.22
Mutation Taster		=94/6	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: rs779741867; hg19: chr6-109787551;