Variant 19-22391581-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001098626.2(ZNF98):c.1654A>G(p.Asn552Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000498 in 1,605,258 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 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

ZNF98
NM_001098626.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.130

Variant links:

Genes affected

ZNF98 (HGNC:13174): (zinc finger protein 98) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF98 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.032926857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF98	NM_001098626.2 linkuse as main transcript	c.1654A>G	p.Asn552Asp	missense_variant	4/4	ENST00000357774.9	NP_001092096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF98	ENST00000357774.9 linkuse as main transcript	c.1654A>G	p.Asn552Asp	missense_variant	4/4	1	NM_001098626.2	ENSP00000350418	P1

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000206

AC:

AN:

193908

Hom.:

AF XY:

0.0000191

AC XY:

AN XY:

104620

show subpopulations

Gnomad AFR exome

AF:

0.000155

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:

0.0000118

Gnomad OTH exome

AF:

0.000206

GnomAD4 exome

AF:

0.0000447

AC:

AN:

1453112

Hom.:

Cov.:

AF XY:

0.0000471

AC XY:

AN XY:

722200

show subpopulations

Gnomad4 AFR exome

AF:

0.000661

Gnomad4 AMR exome

AF:

0.0000233

Gnomad4 ASJ exome

AF:

0.000388

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.000233

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000480

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.0000168

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

Apr 06, 2022

The c.1654A>G (p.N552D) alteration is located in exon 4 (coding exon 4) of the ZNF98 gene. This alteration results from a A to G substitution at nucleotide position 1654, causing the asparagine (N) at amino acid position 552 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

0.064

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.9

DANN

Benign

0.70

DEOGEN2

Benign

0.0023

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.069

M_CAP

Benign

0.0015

MetaRNN

Benign

0.033

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.11

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

0.23

REVEL

Benign

0.017

Sift

Benign

0.21

Sift4G

Benign

0.087

Polyphen

0.0

Vest4

0.15

MVP

0.13

MPC

0.98

ClinPred

0.0047

GERP RS

-2.8

Varity_R

0.038

gMVP

0.0030

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