Genetic Variant ZNF284:p.Gln115Glu (chr19-44085821-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001037813.4(ZNF284):c.343C>G(p.Gln115Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,607,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ZNF284
NM_001037813.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.120

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056338906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF284	NM_001037813.4 link	c.343C>G	p.Gln115Glu	missense_variant	Exon 5 of 5	ENST00000421176.4	NP_001032902.1	Q2VY69
ZNF284	XM_011526907.4 link	c.343C>G	p.Gln115Glu	missense_variant	Exon 5 of 5		XP_011525209.1	Q2VY69
ZNF284	XM_011526908.4 link	c.343C>G	p.Gln115Glu	missense_variant	Exon 6 of 6		XP_011525210.1	Q2VY69
ZNF284	XM_024451486.2 link	c.343C>G	p.Gln115Glu	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.343C>G	p.Gln115Glu	missense_variant	Exon 5 of 5	1	NM_001037813.4	ENSP00000411032.2	Q2VY69
ENSG00000267022	ENST00000591793.1 link	n.*389C>G		non_coding_transcript_exon_variant	Exon 11 of 11	2		ENSP00000467018.1	K7ENM7
ENSG00000267022	ENST00000591793.1 link	n.*389C>G		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000467018.1	K7ENM7

Frequencies

GnomAD3 genomes

AF:

0.0000205

AC:

AN:

146050

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:

0.000592

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:

0.0000200

AC:

AN:

250622

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135558

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

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:

0.0000137

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000479

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000205

AC:

AN:

146050

Hom.:

Cov.:

AF XY:

0.0000282

AC XY:

AN XY:

71030

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000592

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.343C>G (p.Q115E) 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 343, causing the glutamine (Q) at amino acid position 115 to be replaced by a glutamic acid (E). 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

0.074

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0063

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.70

M_CAP

Benign

0.0030

MetaRNN

Benign

0.056

MetaSVM

Benign

-0.93

MutationAssessor

Benign

2.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.9

REVEL

Benign

0.021

Sift

Benign

0.056

Sift4G

Benign

0.31

Polyphen

0.28

Vest4

0.086

MutPred

0.29

Gain of glycosylation at S117 (P = 0.0699);

MVP

0.15

MPC

0.15

ClinPred

0.034

GERP RS

-0.69

Varity_R

0.094

gMVP

0.014

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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