6-33315143-A-T

Position:

• chr6-33315143-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005453.5(ZBTB22):​c.1774T>A​(p.Ser592Thr) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZBTB22 NM_005453.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.468

Genes affected

ZBTB22 (HGNC:13085): (zinc finger and BTB domain containing 22) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093854845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB22	NM_005453.5	c.1774T>A	p.Ser592Thr	missense_variant	2/2	ENST00000431845.3	NP_005444.4
ZBTB22	NM_001145338.2	c.1774T>A	p.Ser592Thr	missense_variant	2/2		NP_001138810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB22	ENST00000431845.3	c.1774T>A	p.Ser592Thr	missense_variant	2/2	1	NM_005453.5	ENSP00000407545	P1
ZBTB22	ENST00000418724.1	c.1774T>A	p.Ser592Thr	missense_variant	2/2	1		ENSP00000404403	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.1774T>A (p.S592T) alteration is located in exon 2 (coding exon 1) of the ZBTB22 gene. This alteration results from a T to A substitution at nucleotide position 1774, causing the serine (S) at amino acid position 592 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.0097	T;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.57	T;.
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.094	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.55	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.16	N;N
REVEL	Benign	0.066
Sift	Uncertain	0.0080	D;D
Sift4G	Benign	0.48	T;T
Polyphen		0.61	P;P
Vest4		0.085
MutPred		0.19		Gain of glycosylation at S592 (P = 0.0337);Gain of glycosylation at S592 (P = 0.0337);
MVP		0.35
MPC		0.55
ClinPred		0.18	T
GERP RS		3.0
Varity_R		0.091
gMVP		0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs1769746082; hg19: chr6-33282920;