17-7462323-C-T

Variant names:

• chr17-7462323-C-T
• NM_001128833.2:c.2659G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001128833.2(ZBTB4):​c.2659G>A​(p.Gly887Ser) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZBTB4 NM_001128833.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.171
• Publications: 0 publications found

Genes affected

ZBTB4 (HGNC:23847): (zinc finger and BTB domain containing 4) Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; methyl-CpNpG binding activity; and sequence-specific DNA binding activity. Involved in cellular response to DNA damage stimulus and negative regulation of transcription by RNA polymerase II. Located in cytosol and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.047541767).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128833.2. 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
	ZBTB4	NM_001128833.2	MANE Select	c.2659G>A	p.Gly887Ser	missense	Exon 4 of 4	NP_001122305.1	Q9P1Z0
	ZBTB4	NM_020899.4		c.2659G>A	p.Gly887Ser	missense	Exon 4 of 4	NP_065950.2	Q9P1Z0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB4	ENST00000380599.9	TSL:1 MANE Select	c.2659G>A	p.Gly887Ser	missense	Exon 4 of 4	ENSP00000369973.4	Q9P1Z0
	ZBTB4	ENST00000311403.4	TSL:1	c.2659G>A	p.Gly887Ser	missense	Exon 4 of 4	ENSP00000307858.4	Q9P1Z0
	ZBTB4	ENST00000907857.1		c.2659G>A	p.Gly887Ser	missense	Exon 4 of 4	ENSP00000577916.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.3
DANN	Benign	0.77
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.095	N
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.17
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.017
Sift	Benign	0.24	T
Sift4G	Benign	0.75	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.17		Gain of phosphorylation at G887 (P = 0.002)
MVP		0.14
MPC		0.45
ClinPred		0.074	T
GERP RS		-3.4
Varity_R		0.025
gMVP		0.24

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

hg19: chr17-7365642;