Variant 9-126880610-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001099270.4(ZBTB34):c.1211T>A(p.Phe404Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,190 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Consequence

ZBTB34
NM_001099270.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

Variant links:

Genes affected

ZBTB34 (HGNC:31446): (zinc finger and BTB domain containing 34) Predicted to enable DNA-binding transcription repressor 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. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB34 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB34	NM_001099270.4 linkuse as main transcript	c.1211T>A	p.Phe404Tyr	missense_variant	2/2	ENST00000319119.5	NP_001092740.2	Q8NCN2
ZBTB34	NM_001395198.1 linkuse as main transcript	c.1241T>A	p.Phe414Tyr	missense_variant	3/3		NP_001382127.1
ZBTB34	XM_047423402.1 linkuse as main transcript	c.1241T>A	p.Phe414Tyr	missense_variant	3/3		XP_047279358.1
ZBTB34	XM_011518699.4 linkuse as main transcript	c.1211T>A	p.Phe404Tyr	missense_variant	2/2		XP_011517001.1	Q8NCN2A0A0C4DFQ2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB34	ENST00000319119.5 linkuse as main transcript	c.1211T>A	p.Phe404Tyr	missense_variant	2/2	1	NM_001099270.4	ENSP00000317534.4		A0A0C4DFQ2
ZBTB34	ENST00000695642.1 linkuse as main transcript	c.1241T>A	p.Phe414Tyr	missense_variant	3/3			ENSP00000512077.1		A0A8Q3WKM1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

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:

0.00

Bravo

AF:

0.00000756

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

Sep 19, 2022

The c.1199T>A (p.F400Y) alteration is located in exon 2 (coding exon 1) of the ZBTB34 gene. This alteration results from a T to A substitution at nucleotide position 1199, causing the phenylalanine (F) at amino acid position 400 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

Pathogenic

0.59

BayesDel_addAF

Uncertain

0.015

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

.;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.63

D;D

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.48

.;N

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-1.0

N;N

REVEL

Uncertain

0.30

Sift

Benign

0.26

T;T

Sift4G

Benign

0.40

T;T

Polyphen

1.0

.;D

Vest4

0.65

MutPred

0.74

.;Gain of catalytic residue at M395 (P = 0.0155);

MVP

0.45

MPC

1.9

ClinPred

0.80

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.21

gMVP

0.83

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