Variant 19-11831712-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000304060.10(ZNF440):c.536A>G(p.Lys179Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,614,108 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 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ZNF440
ENST00000304060.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.22

Variant links:

Genes affected

ZNF440 (HGNC:20874): (zinc finger protein 440) 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. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF440 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=0.2358827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF440	NM_152357.3 linkuse as main transcript	c.536A>G	p.Lys179Arg	missense_variant	4/4	ENST00000304060.10	NP_689570.2	Q8IYI8
ZNF440	XM_005259731.5 linkuse as main transcript	c.545A>G	p.Lys182Arg	missense_variant	4/4		XP_005259788.1
ZNF440	XM_047438145.1 linkuse as main transcript	c.542A>G	p.Lys181Arg	missense_variant	4/4		XP_047294101.1
ZNF440	XM_017026254.2 linkuse as main transcript	c.170A>G	p.Lys57Arg	missense_variant	3/3		XP_016881743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF440	ENST00000304060.10 linkuse as main transcript	c.536A>G	p.Lys179Arg	missense_variant	4/4	1	NM_152357.3	ENSP00000305373.5	Q8IYI8
ZNF440	ENST00000427505.5 linkuse as main transcript	c.545A>G	p.Lys182Arg	missense_variant	4/4	3		ENSP00000393489.1	C9JV94
ZNF440	ENST00000414255.1 linkuse as main transcript	c.*34A>G		downstream_gene_variant		2		ENSP00000411974.1	C9J3D9
ZNF440	ENST00000457526.1 linkuse as main transcript	c.*11A>G		downstream_gene_variant		4		ENSP00000404425.1	C9JG89

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152162

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

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251302

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.0000579

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:

0.00000342

AC:

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000671

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:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000963

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:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

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 17, 2023

The c.536A>G (p.K179R) alteration is located in exon 4 (coding exon 4) of the ZNF440 gene. This alteration results from a A to G substitution at nucleotide position 536, causing the lysine (K) at amino acid position 179 to be replaced by an arginine (R). 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

0.14

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.070

T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.000060

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

0.99

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.13

Sift

Uncertain

0.018

D;D

Sift4G

Uncertain

0.013

D;D

Polyphen

0.99

D;.

Vest4

0.079

MVP

0.62

MPC

0.17

ClinPred

0.30

GERP RS

1.4

Varity_R

0.18

gMVP

0.011

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