chr20-63747139-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001369741.1(ZBTB46):​c.1561G>A​(p.Glu521Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000342 in 1,609,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: ZBTB46 NM_001369741.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15197712).

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>A	p.Glu521Lys	missense	Exon 5 of 5	NP_001356670.1	Q86UZ6
	ZBTB46	NM_025224.4		c.1561G>A	p.Glu521Lys	missense	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>A	p.Glu521Lys	missense	Exon 5 of 5	ENSP00000245663.3	Q86UZ6
	ZBTB46	ENST00000395104.5	TSL:2	c.1561G>A	p.Glu521Lys	missense	Exon 4 of 4	ENSP00000378536.1	Q86UZ6
	ZBTB46	ENST00000906793.1		c.1561G>A	p.Glu521Lys	missense	Exon 5 of 5	ENSP00000576852.1

Frequencies

GnomAD3 genomes AF: 0.0000527 AC: 8 AN: 151924 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000689 AC: 16 AN: 232128 AF XY: 0.0000469

Gnomad AFR exome AF: 0.000144

Gnomad AMR exome AF: 0.000265

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000570

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000396

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000316 AC: 46 AN: 1457404 Hom.: 0 Cov.: 43 AF XY: 0.0000276 AC XY: 20 AN XY: 724916

African (AFR) AF: 0.000239 AC: 8 AN: 33422

American (AMR) AF: 0.000247 AC: 11 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26018

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50938

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5726

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1110854

Other (OTH) AF: 0.0000166 AC: 1 AN: 60116

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152042 Hom.: 0 Cov.: 28 AF XY: 0.0000269 AC XY: 2 AN XY: 74322

African (AFR) AF: 0.0000723 AC: 3 AN: 41486

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5096

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67948

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.0000568 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000420 AC: 5

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		4.0
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.080
Sift	Benign	0.046	D
Sift4G	Benign	0.13	T
Polyphen		0.58	P
Vest4		0.34
MutPred		0.44		Gain of ubiquitination at E521 (P = 0.0054)
MVP		0.068
MPC		0.11
ClinPred		0.042	T
GERP RS		4.0
Varity_R		0.19
gMVP		0.33
Mutation Taster		=76/24	polymorphism

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;