Variant 1-23367097-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000314011.9(ZNF436):c.105G>T(p.Gln35His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,614,030 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 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ZNF436
ENST00000314011.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.431

Variant links:

Genes affected

ZNF436 (HGNC:20814): (zinc finger protein 436) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF436 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, 0.864

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF436	NM_001077195.2 linkuse as main transcript	c.105G>T	p.Gln35His	missense_variant	3/4	ENST00000314011.9	NP_001070663.1
ZNF436	NM_030634.3 linkuse as main transcript	c.105G>T	p.Gln35His	missense_variant	2/3		NP_085137.1
ZNF436	NM_001370652.1 linkuse as main transcript	c.51G>T	p.Gln17His	missense_variant	2/3		NP_001357581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF436	ENST00000314011.9 linkuse as main transcript	c.105G>T	p.Gln35His	missense_variant	3/4	1	NM_001077195.2	ENSP00000313582	P1
ZNF436	ENST00000374608.3 linkuse as main transcript	c.105G>T	p.Gln35His	missense_variant	2/3	1		ENSP00000363736	P1
ZNF436	ENST00000711404.1 linkuse as main transcript	c.51G>T	p.Gln17His	missense_variant	2/3			ENSP00000518729

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

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:

0.000956

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251404

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461776

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.000105

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000915

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:

0.000946

Bravo

AF:

0.000159

ExAC

AF:

0.0000165

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

Dec 18, 2023

The c.105G>T (p.Q35H) alteration is located in exon 3 (coding exon 2) of the ZNF436 gene. This alteration results from a G to T substitution at nucleotide position 105, causing the glutamine (Q) at amino acid position 35 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

0.92

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.44

M_CAP

Benign

0.011

MetaRNN

Pathogenic

0.86

D;D

MetaSVM

Benign

-0.94

MutationAssessor

Pathogenic

3.7

H;H

MutationTaster

Benign

0.75

D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.9

D;D

REVEL

Benign

0.26

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.010

D;D

Polyphen

0.98

D;D

Vest4

0.81

MutPred

0.83

Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);

MVP

0.54

MPC

0.53

ClinPred

0.98

GERP RS

-1.4

Varity_R

0.73

gMVP

0.93

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