Genetic Variant ZNF90:p.Pro62Leu (chr19-20105275-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_007138.2(ZNF90):c.185C>T(p.Pro62Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000379 in 1,607,930 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P62A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ZNF90
NM_007138.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.642

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024561763).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007138.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF90	NM_007138.2	MANE Select	c.185C>T	p.Pro62Leu	missense	Exon 3 of 4	NP_009069.1	Q03938

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF90	ENST00000418063.3	TSL:1 MANE Select	c.185C>T	p.Pro62Leu	missense	Exon 3 of 4	ENSP00000410466.2	Q03938
ZNF90	ENST00000469078.5	TSL:5	n.185C>T		non_coding_transcript_exon	Exon 3 of 6	ENSP00000420111.1	F8WDJ7
ZNF90	ENST00000473524.5	TSL:3	n.185C>T		non_coding_transcript_exon	Exon 3 of 5	ENSP00000418166.1	F8WBQ5

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000561

AC:

AN:

249620

AF XY:

0.0000369

show subpopulations

Gnomad AFR exome

AF:

0.000902

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1455732

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

724270

show subpopulations

African (AFR)

AF:

0.000541

AC:

AN:

33242

American (AMR)

AF:

0.000113

AC:

AN:

44228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25926

East Asian (EAS)

AF:

0.00

AC:

AN:

39402

South Asian (SAS)

AF:

0.00

AC:

AN:

86040

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108748

Other (OTH)

AF:

0.0000167

AC:

AN:

60018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000237

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.000626

AC:

AN:

41536

American (AMR)

AF:

0.000589

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000660

Hom.:

Bravo

AF:

0.000302

ESP6500AA

AF:

0.00145

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000989

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.025

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.81

M_CAP

Benign

0.0019

MetaRNN

Benign

0.025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

0.64

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-7.4

REVEL

Benign

0.046

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.036

Polyphen

0.69

Vest4

0.20

MVP

0.41

MPC

0.0029

ClinPred

0.14

GERP RS

0.54

Varity_R

0.11

gMVP

0.013

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over