6-151365976-C-T

Variant names:

• chr6-151365976-C-T
• NM_020861.3:c.1090G>A

Variant summary

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

The NM_020861.3(ZBTB2):​c.1090G>A​(p.Glu364Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZBTB2 NM_020861.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.79

Genes affected

ZBTB2 (HGNC:20868): (zinc finger and BTB domain containing 2) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and identical protein binding activity. Involved in negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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 rank	MANE	Protein	UniProt
ZBTB2	NM_020861.3	c.1090G>A	p.Glu364Lys	missense_variant	Exon 3 of 3	ENST00000325144.5	NP_065912.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB2	ENST00000325144.5	c.1090G>A	p.Glu364Lys	missense_variant	Exon 3 of 3	1	NM_020861.3	ENSP00000323183.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461890 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1090G>A (p.E364K) alteration is located in exon 3 (coding exon 2) of the ZBTB2 gene. This alteration results from a G to A substitution at nucleotide position 1090, causing the glutamic acid (E) at amino acid position 364 to be replaced by a lysine (K). 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	0.94
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.97	L
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.21
Sift	Benign	0.33	T
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.58
MutPred		0.47		Gain of methylation at E364 (P = 0);
MVP		0.39
MPC		1.6
ClinPred		0.82	D
GERP RS		5.8
Varity_R		0.19
gMVP		0.80

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: chr6-151687111;