dbSNP rs762988227: ZBTB46:p.Gly532Arg (chr20-63747106-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001369741.1(ZBTB46):c.1594G>A(p.Gly532Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,609,934 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G532E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ZBTB46
NM_001369741.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.90

Publications

0 publications found

Variant links:

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]

ZBTB46 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.41166928).

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.1594G>A	p.Gly532Arg	missense	Exon 5 of 5	NP_001356670.1	Q86UZ6
	ZBTB46	NM_025224.4		c.1594G>A	p.Gly532Arg	missense	Exon 5 of 5	NP_079500.2	Q86UZ6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBTB46	ENST00000245663.9	TSL:5 MANE Select	c.1594G>A	p.Gly532Arg	missense	Exon 5 of 5	ENSP00000245663.3	Q86UZ6
ZBTB46	ENST00000395104.5	TSL:2	c.1594G>A	p.Gly532Arg	missense	Exon 4 of 4	ENSP00000378536.1	Q86UZ6
ZBTB46	ENST00000906793.1		c.1594G>A	p.Gly532Arg	missense	Exon 5 of 5	ENSP00000576852.1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000332

AC:

AN:

240724

AF XY:

0.0000532

show subpopulations

Gnomad AFR exome

AF:

0.0000652

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000498

Gnomad NFE exome

AF:

0.0000187

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1457974

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

725476

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.000128

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50196

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111588

Other (OTH)

AF:

0.0000332

AC:

AN:

60292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151960

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41378

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5106

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67976

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000498

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.016

Eigen

Benign

-0.067

Eigen_PC

Benign

-0.086

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.73

M_CAP

Benign

0.048

MetaRNN

Benign

0.41

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

2.9

PrimateAI

Uncertain

0.78

PROVEAN

Benign

0.60

REVEL

Benign

0.085

Sift

Benign

0.28

Sift4G

Benign

0.99

Polyphen

0.90

Vest4

0.59

MutPred

0.41

Loss of sheet (P = 0.1158)

MVP

0.068

MPC

0.32

ClinPred

0.13

GERP RS

3.2

Varity_R

0.11

gMVP

0.29

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over