20-63747139-C-A

Variant names:

• chr20-63747139-C-A
• rs759004681
• NM_001369741.1:c.1561G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001369741.1(ZBTB46):​c.1561G>T​(p.Glu521*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 28)
• Consequence: ZBTB46 NM_001369741.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.01
• Publications: 0 publications found

Genes affected

ZBTB46 (HGNC:16094): (zinc finger and BTB domain containing 46) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within regulation of leukocyte differentiation. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369741.1. 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
	ZBTB46	NM_001369741.1	MANE Select	c.1561G>T	p.Glu521*	stop_gained	Exon 5 of 5	NP_001356670.1	Q86UZ6
	ZBTB46	NM_025224.4		c.1561G>T	p.Glu521*	stop_gained	Exon 5 of 5	NP_079500.2	Q86UZ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB46	ENST00000245663.9	TSL:5 MANE Select	c.1561G>T	p.Glu521*	stop_gained	Exon 5 of 5	ENSP00000245663.3	Q86UZ6
	ZBTB46	ENST00000395104.5	TSL:2	c.1561G>T	p.Glu521*	stop_gained	Exon 4 of 4	ENSP00000378536.1	Q86UZ6
	ZBTB46	ENST00000906793.1		c.1561G>T	p.Glu521*	stop_gained	Exon 5 of 5	ENSP00000576852.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 43

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.56
CADD	Pathogenic	38
DANN	Uncertain	1.0
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.86	D
PhyloP100		4.0
Vest4		0.056
GERP RS		4.0
Mutation Taster		=37/163	disease causing

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

dbSNP: rs759004681; hg19: chr20-62378492;