Variant chr14-64523129-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001123329.2(ZBTB1):c.1625G>A(p.Arg542His) variant causes a missense change. The variant allele was found at a frequency of 0.000183 in 1,614,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

ZBTB1
NM_001123329.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.85

Variant links:

Genes affected

ZBTB1 (HGNC:20259): (zinc finger and BTB domain containing 1) Enables K63-linked polyubiquitin modification-dependent protein binding activity; protein heterodimerization activity; and protein homodimerization activity. Involved in several processes, including cellular response to UV; nucleobase-containing compound biosynthetic process; and protein homooligomerization. Located in centrosome; nuclear body; and nuclear membrane. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB1 links:

HSPA2-AS1 (HGNC:55433): (HSPA2 and ZBTB1 antisense RNA 1)

HSPA2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.070191294).

BS2

High AC in GnomAd4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB1	NM_001123329.2 linkuse as main transcript	c.1625G>A	p.Arg542His	missense_variant	2/2	ENST00000683701.1	NP_001116801.1
HSPA2-AS1	NR_110550.1 linkuse as main transcript	n.149-4591C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB1	ENST00000683701.1 linkuse as main transcript	c.1625G>A	p.Arg542His	missense_variant	2/2		NM_001123329.2	ENSP00000506911	P1	Q9Y2K1-1
HSPA2-AS1	ENST00000554918.1 linkuse as main transcript	n.149-4591C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000207

AC:

AN:

251334

Hom.:

AF XY:

0.000191

AC XY:

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000431

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000187

AC:

274

AN:

1461850

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

128

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000225

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000144

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000190

Hom.:

Bravo

AF:

0.000106

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000288

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 01, 2024

The c.1625G>A (p.R542H) alteration is located in exon 2 (coding exon 1) of the ZBTB1 gene. This alteration results from a G to A substitution at nucleotide position 1625, causing the arginine (R) at amino acid position 542 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

T;.

Eigen

Benign

-0.066

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.0069

MetaRNN

Benign

0.070

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;L

MutationTaster

Benign

0.96

D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.079

Sift

Benign

0.37

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.0070

B;B

Vest4

0.30

MVP

0.24

ClinPred

0.14

GERP RS

5.0

Varity_R

0.13

gMVP

0.36

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