Variant 19-22391866-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001098626.2(ZNF98):c.1369A>G(p.Thr457Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000057 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF98
NM_001098626.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.693

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.15069914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF98	NM_001098626.2 linkuse as main transcript	c.1369A>G	p.Thr457Ala	missense_variant	4/4	ENST00000357774.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF98	ENST00000357774.9 linkuse as main transcript	c.1369A>G	p.Thr457Ala	missense_variant	4/4	1	NM_001098626.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

133958

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000233

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000805

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000570

AC:

AN:

1386498

Hom.:

Cov.:

AF XY:

0.0000594

AC XY:

AN XY:

690532

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.00

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:

0.0000726

Gnomad4 OTH exome

AF:

0.0000175

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000448

AC:

AN:

134044

Hom.:

Cov.:

AF XY:

0.0000619

AC XY:

AN XY:

64598

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000234

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000805

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000397

Hom.:

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

Aug 16, 2022

The c.1369A>G (p.T457A) 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 1369, causing the threonine (T) at amino acid position 457 to be replaced by an alanine (A). 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

0.17

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.58

Cadd

Benign

Dann

Uncertain

0.97

DEOGEN2

Benign

0.12

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.040

M_CAP

Benign

0.0067

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.0

MutationTaster

Benign

0.96

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.050

Sift

Uncertain

0.024

Sift4G

Uncertain

0.015

Polyphen

0.49

Vest4

0.15

MutPred

0.34

Loss of ubiquitination at K460 (P = 0.1151);

MVP

0.20

MPC

0.88

ClinPred

0.14

GERP RS

-0.042

Varity_R

0.098

gMVP

0.0069

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