20-63747082-C-A

Variant names:

• chr20-63747082-C-A
• rs1290756472
• NM_001369741.1:c.1618G>T

Variant summary

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

The NM_001369741.1(ZBTB46):​c.1618G>T​(p.Asp540Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,609,196 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: ZBTB46 NM_001369741.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.11
• 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 0 ACMG points.

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.1618G>T	p.Asp540Tyr	missense	Exon 5 of 5	NP_001356670.1	Q86UZ6
	ZBTB46	NM_025224.4		c.1618G>T	p.Asp540Tyr	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.1618G>T	p.Asp540Tyr	missense	Exon 5 of 5	ENSP00000245663.3	Q86UZ6
	ZBTB46	ENST00000395104.5	TSL:2	c.1618G>T	p.Asp540Tyr	missense	Exon 4 of 4	ENSP00000378536.1	Q86UZ6
	ZBTB46	ENST00000906793.1		c.1618G>T	p.Asp540Tyr	missense	Exon 5 of 5	ENSP00000576852.1

Frequencies

GnomAD3 genomes AF: 0.0000790 AC: 12 AN: 151962 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.00000892 AC: 13 AN: 1457234 Hom.: 0 Cov.: 43 AF XY: 0.00000965 AC XY: 7 AN XY: 725132

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.000112 AC: 5 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111524

Other (OTH) AF: 0.000133 AC: 8 AN: 60308

GnomAD4 genome AF: 0.0000790 AC: 12 AN: 151962 Hom.: 0 Cov.: 28 AF XY: 0.0000809 AC XY: 6 AN XY: 74210

African (AFR) AF: 0.0000242 AC: 1 AN: 41384

American (AMR) AF: 0.000654 AC: 10 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5090

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67984

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000329

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	0.28
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.66	T
M_CAP	Uncertain	0.089	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		7.1
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.12
Sift	Uncertain	0.026	D
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.51
MutPred		0.34		Gain of phosphorylation at D540 (P = 0.0135)
MVP		0.068
MPC		0.44
ClinPred		0.93	D
GERP RS		4.0
Varity_R		0.22
gMVP		0.48
Mutation Taster		=61/39	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: rs1290756472; hg19: chr20-62378435;