Variant chr1-6581288-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000377674.9(ZBTB48):c.679G>A(p.Gly227Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00825 in 1,601,828 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0069 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0084 ( 85 hom. )

Consequence

ZBTB48
ENST00000377674.9 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.549

Variant links:

Genes affected

ZBTB48 (HGNC:4930): (zinc finger and BTB domain containing 48) Enables double-stranded telomeric DNA binding activity; identical protein binding activity; and transcription cis-regulatory region binding activity. Involved in positive regulation of transcription, DNA-templated and telomere maintenance via telomere lengthening. Located in chromosome, telomeric region. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB48 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023840368).

BP6

Variant 1-6581288-G-A is Benign according to our data. Variant chr1-6581288-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2638126.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB48	NM_005341.4 linkuse as main transcript	c.679G>A	p.Gly227Ser	missense_variant	2/11	ENST00000377674.9	NP_005332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZBTB48	ENST00000377674.9 linkuse as main transcript	c.679G>A	p.Gly227Ser	missense_variant	2/11	1	NM_005341.4	ENSP00000366902.4	P10074
ZBTB48	ENST00000319084.9 linkuse as main transcript	c.679G>A	p.Gly227Ser	missense_variant	2/3	3		ENSP00000313416.5	Q5SY20
ZBTB48	ENST00000435905.5 linkuse as main transcript	c.679G>A	p.Gly227Ser	missense_variant	2/3	5		ENSP00000416054.1	Q5SY21
ZBTB48	ENST00000488936.1 linkuse as main transcript	c.-45-770G>A		intron_variant		3		ENSP00000466390.1	K7EM76

Frequencies

GnomAD3 genomes

AF:

0.00687

AC:

1046

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00434

Gnomad FIN

AF:

0.0261

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00899

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00788

AC:

1872

AN:

237432

Hom.:

AF XY:

0.00784

AC XY:

1017

AN XY:

129802

show subpopulations

Gnomad AFR exome

AF:

0.00168

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00187

Gnomad EAS exome

AF:

0.0000560

Gnomad SAS exome

AF:

0.00402

Gnomad FIN exome

AF:

0.0262

Gnomad NFE exome

AF:

0.0102

Gnomad OTH exome

AF:

0.00695

GnomAD4 exome

AF:

0.00840

AC:

12175

AN:

1449548

Hom.:

Cov.:

AF XY:

0.00834

AC XY:

6014

AN XY:

720722

show subpopulations

Gnomad4 AFR exome

AF:

0.00103

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.00216

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00371

Gnomad4 FIN exome

AF:

0.0276

Gnomad4 NFE exome

AF:

0.00891

Gnomad4 OTH exome

AF:

0.00702

GnomAD4 genome

AF:

0.00688

AC:

1047

AN:

152280

Hom.:

Cov.:

AF XY:

0.00728

AC XY:

542

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.0261

Gnomad4 NFE

AF:

0.00900

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00758

Hom.:

Bravo

AF:

0.00505

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.00849

AC:

ExAC

AF:

0.00847

AC:

1027

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

ZBTB48: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.044

.;.;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.62

T;T;T

MetaRNN

Benign

0.0024

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.95

PrimateAI

Benign

0.28

PROVEAN

Benign

0.030

N;N;N

REVEL

Benign

0.0050

Sift

Benign

0.33

T;T;T

Sift4G

Benign

0.72

T;T;T

Polyphen

0.41

.;.;B

Vest4

0.074

MVP

0.043

MPC

0.40

ClinPred

0.0037

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.044

gMVP

0.094

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over