Variant chr1-197181090-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_194314.3(ZBTB41):c.1574G>A(p.Arg525His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,597,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

ZBTB41
NM_194314.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.46

Variant links:

Genes affected

ZBTB41 (HGNC:24819): (zinc finger and BTB domain containing 41) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB41 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.853

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB41	NM_194314.3 linkuse as main transcript	c.1574G>A	p.Arg525His	missense_variant	6/11	ENST00000367405.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB41	ENST00000367405.5 linkuse as main transcript	c.1574G>A	p.Arg525His	missense_variant	6/11	1	NM_194314.3	P1	Q5SVQ8-1
ZBTB41	ENST00000467322.1 linkuse as main transcript	c.1574G>A	p.Arg525His	missense_variant, NMD_transcript_variant	5/11	2			Q5SVQ8-2

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

151004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000899

AC:

AN:

1446706

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

719686

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000587

Gnomad4 NFE exome

AF:

0.00000812

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000199

AC:

AN:

151122

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73782

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000210

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Aug 04, 2023

The c.1574G>A (p.R525H) alteration is located in exon 5 (coding exon 5) of the ZBTB41 gene. This alteration results from a G to A substitution at nucleotide position 1574, causing the arginine (R) at amino acid position 525 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

Pathogenic

0.85

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.021

MetaRNN

Pathogenic

0.85

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.95

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.52

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.75

MutPred

0.68

Gain of relative solvent accessibility (P = 0.2363);

MVP

0.67

MPC

2.7

ClinPred

0.99

GERP RS

5.5

Varity_R

0.37

gMVP

0.76

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