Genetic Variant ZNF284:p.Pro94Arg (chr19-44085759-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001037813.4(ZNF284):c.281C>G(p.Pro94Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ZNF284
NM_001037813.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0390

Variant links:

Genes affected

ZNF284 (HGNC:13078): (zinc finger protein 284) 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]

ZNF284 links:

ENSG00000267022 (HGNC:):

ENSG00000267022 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0785383).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF284	NM_001037813.4 link	c.281C>G	p.Pro94Arg	missense_variant	Exon 5 of 5	ENST00000421176.4	NP_001032902.1	Q2VY69
ZNF284	XM_011526907.4 link	c.281C>G	p.Pro94Arg	missense_variant	Exon 5 of 5		XP_011525209.1	Q2VY69
ZNF284	XM_011526908.4 link	c.281C>G	p.Pro94Arg	missense_variant	Exon 6 of 6		XP_011525210.1	Q2VY69
ZNF284	XM_024451486.2 link	c.281C>G	p.Pro94Arg	missense_variant	Exon 5 of 5		XP_024307254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF284	ENST00000421176.4 link	c.281C>G	p.Pro94Arg	missense_variant	Exon 5 of 5	1	NM_001037813.4	ENSP00000411032.2	Q2VY69
ENSG00000267022	ENST00000591793.1 link	n.*327C>G		non_coding_transcript_exon_variant	Exon 11 of 11	2		ENSP00000467018.1	K7ENM7
ENSG00000267022	ENST00000591793.1 link	n.*327C>G		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000467018.1	K7ENM7

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

250838

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135624

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

Gnomad SAS 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:

0.00000479

AC:

AN:

1461726

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.281C>G (p.P94R) alteration is located in exon 5 (coding exon 4) of the ZNF284 gene. This alteration results from a C to G substitution at nucleotide position 281, causing the proline (P) at amino acid position 94 to be replaced by an arginine (R). 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

0.10

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.049

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.33

M_CAP

Benign

0.0038

MetaRNN

Benign

0.079

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.042

Sift

Benign

0.11

Sift4G

Benign

0.23

Polyphen

0.96

Vest4

0.12

MutPred

0.18

Loss of glycosylation at P94 (P = 0.0886);

MVP

0.26

MPC

0.16

ClinPred

0.34

GERP RS

1.9

Varity_R

0.049

gMVP

0.025

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over