Variant 19-43607744-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_182498.4(ZNF428):c.440C>A(p.Ala147Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000969 in 1,610,666 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00073 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00099 ( 3 hom. )

Consequence

ZNF428
NM_182498.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08

Variant links:

Genes affected

ZNF428 (HGNC:20804): (zinc finger protein 428) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZNF428 links:

SRRM5 (HGNC:37248): (serine/arginine repetitive matrix 5)

SRRM5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00845176).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF428	NM_182498.4 linkuse as main transcript	c.440C>A	p.Ala147Asp	missense_variant	3/3	ENST00000300811.8	NP_872304.2
ZNF428	XM_047438168.1 linkuse as main transcript	c.440C>A	p.Ala147Asp	missense_variant	4/4		XP_047294124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF428	ENST00000300811.8 linkuse as main transcript	c.440C>A	p.Ala147Asp	missense_variant	3/3	1	NM_182498.4	ENSP00000300811	P1
ZNF428	ENST00000598676.1 linkuse as main transcript	c.539C>A	p.Ala180Asp	missense_variant	4/4	5		ENSP00000469484
SRRM5	ENST00000607544.1 linkuse as main transcript	c.-95-4283G>T		intron_variant		2		ENSP00000476253	P1

Frequencies

GnomAD3 genomes

AF:

0.000730

AC:

110

AN:

150750

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00126

Gnomad FIN

AF:

0.00181

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000735

AC:

181

AN:

246186

Hom.:

AF XY:

0.000833

AC XY:

111

AN XY:

133314

show subpopulations

Gnomad AFR exome

AF:

0.000127

Gnomad AMR exome

AF:

0.000205

Gnomad ASJ exome

AF:

0.000403

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000862

Gnomad FIN exome

AF:

0.00182

Gnomad NFE exome

AF:

0.000895

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.000993

AC:

1450

AN:

1459798

Hom.:

Cov.:

AF XY:

0.000920

AC XY:

668

AN XY:

726060

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.000180

Gnomad4 ASJ exome

AF:

0.000345

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000965

Gnomad4 FIN exome

AF:

0.00186

Gnomad4 NFE exome

AF:

0.00108

Gnomad4 OTH exome

AF:

0.000763

GnomAD4 genome

AF:

0.000729

AC:

110

AN:

150868

Hom.:

Cov.:

AF XY:

0.000827

AC XY:

AN XY:

73752

show subpopulations

Gnomad4 AFR

AF:

0.000171

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00126

Gnomad4 FIN

AF:

0.00181

Gnomad4 NFE

AF:

0.00109

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000681

Hom.:

Bravo

AF:

0.000518

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000774

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

May 08, 2024

The c.440C>A (p.A147D) alteration is located in exon 3 (coding exon 2) of the ZNF428 gene. This alteration results from a C to A substitution at nucleotide position 440, causing the alanine (A) at amino acid position 147 to be replaced by an aspartic acid (D). 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

0.13

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.074

T;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.59

T;T

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.0085

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.7

D;.

REVEL

Benign

0.035

Sift

Uncertain

0.0070

D;.

Sift4G

Benign

0.35

T;.

Polyphen

0.0060

B;.

Vest4

0.23

MVP

0.043

MPC

0.79

ClinPred

0.051

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.19

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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