chr21-41991527-C-A

Position:

• chr21-41991527-C-A

Variant summary

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

The NM_001098402.2(ZBTB21):​c.2569G>T​(p.Asp857Tyr) variant causes a missense 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: ZBTB21 NM_001098402.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.20

Genes affected

ZBTB21 (HGNC:13083): (zinc finger and BTB domain containing 21) Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; POZ domain binding activity; and methyl-CpG binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB21 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB21	NM_001098402.2	c.2569G>T	p.Asp857Tyr	missense_variant	3/3	ENST00000310826.10	NP_001091872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB21	ENST00000310826.10	c.2569G>T	p.Asp857Tyr	missense_variant	3/3	1	NM_001098402.2	ENSP00000308759.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Apr 09, 2024

The c.2569G>T (p.D857Y) alteration is located in exon 3 (coding exon 1) of the ZBTB21 gene. This alteration results from a G to T substitution at nucleotide position 2569, causing the aspartic acid (D) at amino acid position 857 to be replaced by a tyrosine (Y). 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	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;T;T;T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;.;.;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.56	D;D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.7	.;M;M;M
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.6	D;N;N;N
REVEL	Benign	0.22
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.60
MutPred		0.41		.;Loss of solvent accessibility (P = 0.0052);Loss of solvent accessibility (P = 0.0052);Loss of solvent accessibility (P = 0.0052);
MVP		0.28
MPC		0.80
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.35
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-43411636;