chr19-20105274-C-G

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>G​(p.Pro62Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P62L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ZNF90
NM_007138.2 missense

Scores

1
3
15

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]

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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=0.13006699).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF90NM_007138.2 linkc.184C>G p.Pro62Ala missense_variant Exon 3 of 4 ENST00000418063.3 NP_009069.1 Q03938

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF90ENST00000418063.3 linkc.184C>G p.Pro62Ala missense_variant Exon 3 of 4 1 NM_007138.2 ENSP00000410466.2 Q03938
ZNF90ENST00000469078.5 linkn.184C>G non_coding_transcript_exon_variant Exon 3 of 6 5 ENSP00000420111.1 F8WDJ7
ZNF90ENST00000473524.5 linkn.184C>G non_coding_transcript_exon_variant Exon 3 of 5 3 ENSP00000418166.1 F8WBQ5
ZNF90ENST00000474284.1 linkn.196C>G non_coding_transcript_exon_variant Exon 2 of 4 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 01, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.184C>G (p.P62A) alteration is located in exon 3 (coding exon 3) of the ZNF90 gene. This alteration results from a C to G substitution at nucleotide position 184, causing the proline (P) at amino acid position 62 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
0.12
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
8.8
DANN
Benign
0.71
DEOGEN2
Benign
0.030
T
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.92
FATHMM_MKL
Benign
0.022
N
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.0013
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.8
M
PhyloP100
0.64
PrimateAI
Benign
0.40
T
PROVEAN
Pathogenic
-5.5
D
REVEL
Benign
0.042
Sift
Uncertain
0.027
D
Sift4G
Uncertain
0.021
D
Polyphen
0.24
B
Vest4
0.20
MutPred
0.51
Loss of methylation at K66 (P = 0.0724);
MVP
0.28
MPC
0.0026
ClinPred
0.29
T
GERP RS
0.54
Varity_R
0.061
gMVP
0.0063
Mutation Taster
=92/8
polymorphism

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

Other links and lift over

dbSNP: rs2083393008; hg19: chr19-20216083; API