Variant 19-52321975-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_144684.4(ZNF480):c.725G>A(p.Arg242His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,612,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

ZNF480
NM_144684.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.62

Variant links:

Genes affected

ZNF480 (HGNC:23305): (zinc finger protein 480) Predicted to enable DNA-binding transcription factor 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 cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF480 links:

ENSG00000269535 (HGNC:):

ENSG00000269535 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05381894).

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF480	NM_144684.4 linkuse as main transcript	c.725G>A	p.Arg242His	missense_variant	5/5	ENST00000595962.6	NP_653285.2	Q8WV37-1B7Z8E1
ZNF480	NM_001297624.2 linkuse as main transcript	c.596G>A	p.Arg199His	missense_variant	4/4		NP_001284553.1	Q8WV37F8WEZ9B7Z8E1
ZNF480	NM_001297625.2 linkuse as main transcript	c.494G>A	p.Arg165His	missense_variant	4/4		NP_001284554.1	Q8WV37-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF480	ENST00000595962.6 linkuse as main transcript	c.725G>A	p.Arg242His	missense_variant	5/5	1	NM_144684.4	ENSP00000471754.1		Q8WV37-1
ZNF480	ENST00000468240.6 linkuse as main transcript	n.725G>A		non_coding_transcript_exon_variant	5/6	2		ENSP00000417424.1		Q8WV37-1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000997

AC:

AN:

250628

Hom.:

AF XY:

0.0000885

AC XY:

AN XY:

135520

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000134

AC:

195

AN:

1460052

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

100

AN XY:

726328

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000813

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.000147

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000105

Hom.:

Bravo

AF:

0.0000831

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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 23, 2023

The c.725G>A (p.R242H) alteration is located in exon 5 (coding exon 4) of the ZNF480 gene. This alteration results from a G to A substitution at nucleotide position 725, causing the arginine (R) at amino acid position 242 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

Benign

0.24

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.010

T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00027

LIST_S2

Benign

0.19

T;T;T

M_CAP

Benign

0.00062

MetaRNN

Benign

0.054

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.49

N;.;.

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.1

.;N;N

REVEL

Benign

0.038

Sift

Benign

0.24

.;T;T

Sift4G

Benign

0.094

T;T;T

Polyphen

0.94

P;B;.

Vest4

0.030

MVP

0.061

MPC

0.063

ClinPred

0.0029

GERP RS

-4.2

Varity_R

0.015

gMVP

0.041

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