dbSNP rs142859199: ZNF333:p.Pro134Gln (chr19-14705148-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_032433.4(ZNF333):c.401C>A(p.Pro134Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. P134L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF333
NM_032433.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.227

Publications

0 publications found

Variant links:

Genes affected

ZNF333 (HGNC:15624): (zinc finger protein 333) 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 by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF333 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=0.08433673).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032433.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF333	NM_032433.4	MANE Select	c.401C>A	p.Pro134Gln	missense	Exon 6 of 12	NP_115809.1	Q96JL9-1
ZNF333	NM_001352239.2		c.74C>A	p.Pro25Gln	missense	Exon 7 of 13	NP_001339168.1	B3KSN8
ZNF333	NM_001352240.2		c.74C>A	p.Pro25Gln	missense	Exon 7 of 13	NP_001339169.1	B3KSN8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF333	ENST00000292530.11	TSL:1 MANE Select	c.401C>A	p.Pro134Gln	missense	Exon 6 of 12	ENSP00000292530.5	Q96JL9-1
ZNF333	ENST00000540689.6	TSL:1	c.401C>A	p.Pro134Gln	missense	Exon 6 of 12	ENSP00000438130.1	Q96JL9-3
ZNF333	ENST00000597007.5	TSL:1	n.*394C>A		non_coding_transcript_exon	Exon 7 of 10	ENSP00000471574.1	M0R113

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461346

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726972

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5562

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111884

Other (OTH)

AF:

0.00

AC:

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.8

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0015

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.69

M_CAP

Benign

0.0021

MetaRNN

Benign

0.084

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

PhyloP100

-0.23

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.17

REVEL

Benign

0.0090

Sift

Uncertain

0.011

Sift4G

Benign

0.072

Polyphen

0.36

Vest4

0.28

MutPred

0.33

Loss of glycosylation at P134 (P = 0.048)

MVP

0.088

MPC

0.48

ClinPred

0.25

GERP RS

-0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.063

gMVP

0.30

Mutation Taster

=100/0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over