Genetic Variant ZNF90:p.Gln89His (chr19-20117821-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007138.2(ZNF90):c.267G>C(p.Gln89His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,434,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF90
NM_007138.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.458

Publications

0 publications found

Variant links:

Genes affected

ZNF90 (HGNC:13165): (zinc finger protein 90) 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]

ZNF90 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06912851).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF90	NM_007138.2 link	c.267G>C	p.Gln89His	missense_variant	Exon 4 of 4	ENST00000418063.3	NP_009069.1	Q03938
ZNF90	XM_047439360.1 link	c.39G>C	p.Gln13His	missense_variant	Exon 2 of 2		XP_047295316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF90	ENST00000418063.3 link	c.267G>C	p.Gln89His	missense_variant	Exon 4 of 4	1	NM_007138.2	ENSP00000410466.2		Q03938

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000454

AC:

AN:

220152

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000995

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1434078

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711952

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32258

American (AMR)

AF:

0.00

AC:

AN:

39436

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24378

East Asian (EAS)

AF:

0.00

AC:

AN:

39460

South Asian (SAS)

AF:

0.00

AC:

AN:

80884

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5622

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1100428

Other (OTH)

AF:

0.00

AC:

AN:

59240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 03, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.267G>C (p.Q89H) alteration is located in exon 4 (coding exon 4) of the ZNF90 gene. This alteration results from a G to C substitution at nucleotide position 267, causing the glutamine (Q) at amino acid position 89 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

0.15

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.020

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.63

M_CAP

Benign

0.0017

MetaRNN

Benign

0.069

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.4

PhyloP100

0.46

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.021

Sift

Benign

0.067

Sift4G

Benign

0.065

Polyphen

0.0060

Vest4

0.076

MutPred

0.29

Gain of catalytic residue at L91 (P = 0.0778);

MVP

0.18

MPC

0.0024

ClinPred

0.12

GERP RS

0.49

Varity_R

0.048

gMVP

0.018

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over