21-41991163-G-A

Position:

• chr21-41991163-G-A

Variant summary

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

The NM_001098402.2(ZBTB21):​c.2933C>T​(p.Pro978Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZBTB21 NM_001098402.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.85

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]

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=0.25894004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB21	NM_001098402.2	c.2933C>T	p.Pro978Leu	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.2933C>T	p.Pro978Leu	missense_variant	3/3	1	NM_001098402.2	ENSP00000308759.5
ZBTB21	ENST00000398499.5	c.2933C>T	p.Pro978Leu	missense_variant	4/4	1		ENSP00000381512.1
ZBTB21	ENST00000398511.3	c.2933C>T	p.Pro978Leu	missense_variant	2/2	1		ENSP00000381523.3
ZBTB21	ENST00000398505.7	c.2330C>T	p.Pro777Leu	missense_variant	4/4	1		ENSP00000381517.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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

Sep 07, 2022

The c.2933C>T (p.P978L) alteration is located in exon 3 (coding exon 1) of the ZBTB21 gene. This alteration results from a C to T substitution at nucleotide position 2933, causing the proline (P) at amino acid position 978 to be replaced by a leucine (L). 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	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	.;T;T;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.74	T;.;.;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;L;L;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.5	D;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.14	T;T;T;T
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.29
MutPred		0.20		.;Loss of glycosylation at P978 (P = 0.0583);Loss of glycosylation at P978 (P = 0.0583);Loss of glycosylation at P978 (P = 0.0583);
MVP		0.17
MPC		0.18
ClinPred		0.73	D
GERP RS		5.5
Varity_R		0.081
gMVP		0.38

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: chr21-43411272; COSMIC: COSV60403262; COSMIC: COSV60403262;