dbSNP rs2083393008: ZNF90:p.Pro62Thr (chr19-20105274-C-A) – 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.184C>A(p.Pro62Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,455,846 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ZNF90
NM_007138.2 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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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=0.14371532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF90	NM_007138.2 link	c.184C>A	p.Pro62Thr	missense_variant	Exon 3 of 4	ENST00000418063.3	NP_009069.1	Q03938

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF90	ENST00000418063.3 link	c.184C>A	p.Pro62Thr	missense_variant	Exon 3 of 4	1	NM_007138.2	ENSP00000410466.2	Q03938
ZNF90	ENST00000469078.5 link	n.184C>A		non_coding_transcript_exon_variant	Exon 3 of 6	5		ENSP00000420111.1	F8WDJ7
ZNF90	ENST00000473524.5 link	n.184C>A		non_coding_transcript_exon_variant	Exon 3 of 5	3		ENSP00000418166.1	F8WBQ5
ZNF90	ENST00000474284.1 link	n.196C>A		non_coding_transcript_exon_variant	Exon 2 of 4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1455846

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724286

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33240

American (AMR)

AF:

0.00

AC:

AN:

44238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25924

East Asian (EAS)

AF:

0.00

AC:

AN:

39420

South Asian (SAS)

AF:

0.00

AC:

AN:

86042

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00000631

AC:

AN:

1108840

Other (OTH)

AF:

0.00

AC:

AN:

60018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000414

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.028

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.76

M_CAP

Benign

0.0015

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

0.64

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-5.8

REVEL

Benign

0.042

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.022

Polyphen

0.53

Vest4

0.17

MutPred

0.44

Loss of ubiquitination at K61 (P = 0.0896);

MVP

0.31

MPC

0.0027

ClinPred

0.42

GERP RS

0.54

Varity_R

0.13

gMVP

0.015

Mutation Taster

=92/8

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

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rs2083393008

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over