Variant 1-22502326-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014870.4(ZBTB40):c.1052C>A(p.Ser351Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,613,800 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 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

ZBTB40
NM_014870.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18

Variant links:

Genes affected

ZBTB40 (HGNC:29045): (zinc finger and BTB domain containing 40) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in cellular response to DNA damage stimulus. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB40 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.079532325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB40	NM_014870.4 link	c.1052C>A	p.Ser351Tyr	missense_variant	5/18	ENST00000375647.5	NP_055685.3	Q9NUA8-1Q1RMZ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB40	ENST00000375647.5 link	c.1052C>A	p.Ser351Tyr	missense_variant	5/18	1	NM_014870.4	ENSP00000364798.4		Q9NUA8-1

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000990

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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

GnomAD3 exomes

AF:

0.0000518

AC:

AN:

251192

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000267

AC:

AN:

1461676

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000283

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.000310

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.000990

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000219

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

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

Oct 12, 2021

The c.1052C>A (p.S351Y) alteration is located in exon 6 (coding exon 4) of the ZBTB40 gene. This alteration results from a C to A substitution at nucleotide position 1052, causing the serine (S) at amino acid position 351 to be replaced by a tyrosine (Y). 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

Benign

0.19

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.021

T;T;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.83

T;T;.

M_CAP

Benign

0.021

MetaRNN

Benign

0.080

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.;M

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.23

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0050

D;T;D

Polyphen

0.95

P;.;P

Vest4

0.75

MVP

0.54

MPC

0.40

ClinPred

0.12

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.50

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