Variant chr19-52915318-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001393938.1(ZNF888):c.20T>G(p.Leu7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,612,902 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 36)

Exomes 𝑓: 0.0013 ( 12 hom. )

Consequence

ZNF888
NM_001393938.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.34

Variant links:

Genes affected

ZNF888 (HGNC:38695): (zinc finger protein 888) 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. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF888 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006778419).

BP6

Variant 19-52915318-A-C is Benign according to our data. Variant chr19-52915318-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3024858.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF888	NM_001393938.1 linkuse as main transcript	c.20T>G	p.Leu7Arg	missense_variant	4/5	ENST00000638862.2	NP_001380867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF888	ENST00000638862.2 linkuse as main transcript	c.20T>G	p.Leu7Arg	missense_variant	4/5	5	NM_001393938.1	ENSP00000491567	P1
ZNF888	ENST00000596623.2 linkuse as main transcript	n.429T>G		non_coding_transcript_exon_variant	4/5	5

Frequencies

GnomAD3 genomes

AF:

0.00239

AC:

363

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00663

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00434

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00138

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00161

AC:

396

AN:

246244

Hom.:

AF XY:

0.00161

AC XY:

216

AN XY:

133792

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00416

Gnomad ASJ exome

AF:

0.00677

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000836

Gnomad FIN exome

AF:

0.000653

Gnomad NFE exome

AF:

0.000997

Gnomad OTH exome

AF:

0.00366

GnomAD4 exome

AF:

0.00127

AC:

1861

AN:

1460624

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

992

AN XY:

726632

show subpopulations

Gnomad4 AFR exome

AF:

0.000987

Gnomad4 AMR exome

AF:

0.00444

Gnomad4 ASJ exome

AF:

0.00844

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00144

Gnomad4 FIN exome

AF:

0.000749

Gnomad4 NFE exome

AF:

0.000907

Gnomad4 OTH exome

AF:

0.00297

GnomAD4 genome

AF:

0.00238

AC:

363

AN:

152278

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

193

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00214

Gnomad4 AMR

AF:

0.00662

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00455

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00138

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00350

Hom.:

ESP6500AA

AF:

0.000571

AC:

ESP6500EA

AF:

0.000503

AC:

ExAC

AF:

0.00162

AC:

196

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

ZNF888: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.015

DANN

Benign

0.26

DEOGEN2

Benign

0.012

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.017

MetaRNN

Benign

0.0068

MetaSVM

Benign

-1.0

GERP RS

-4.2

Varity_R

0.071

gMVP

0.037

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