Genetic Variant ZNF284:p.Asn40Asp (chr19-44081117-A-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001037813.4(ZNF284):c.118A>G(p.Asn40Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000164 in 1,460,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ZNF284
NM_001037813.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.70

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.861

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF284	NM_001037813.4 link	c.118A>G	p.Asn40Asp	missense_variant	Exon 3 of 5	ENST00000421176.4	NP_001032902.1	Q2VY69
ZNF284	XM_011526907.4 link	c.118A>G	p.Asn40Asp	missense_variant	Exon 3 of 5		XP_011525209.1	Q2VY69
ZNF284	XM_011526908.4 link	c.118A>G	p.Asn40Asp	missense_variant	Exon 4 of 6		XP_011525210.1	Q2VY69
ZNF284	XM_024451486.2 link	c.118A>G	p.Asn40Asp	missense_variant	Exon 3 of 5		XP_024307254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF284	ENST00000421176.4 link	c.118A>G	p.Asn40Asp	missense_variant	Exon 3 of 5	1	NM_001037813.4	ENSP00000411032.2	Q2VY69
ENSG00000267022	ENST00000591793.1 link	n.*164A>G		non_coding_transcript_exon_variant	Exon 9 of 11	2		ENSP00000467018.1	K7ENM7
ENSG00000267022	ENST00000591793.1 link	n.*164A>G		3_prime_UTR_variant	Exon 9 of 11	2		ENSP00000467018.1	K7ENM7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251322

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1460388

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

726490

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.118A>G (p.N40D) alteration is located in exon 3 (coding exon 2) of the ZNF284 gene. This alteration results from a A to G substitution at nucleotide position 118, causing the asparagine (N) at amino acid position 40 to be replaced by an aspartic acid (D). 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

Pathogenic

0.85

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.045

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.49

M_CAP

Benign

0.0012

MetaRNN

Pathogenic

0.86

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.5

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.17

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.70

MutPred

0.82

Loss of MoRF binding (P = 0.0929);

MVP

0.35

MPC

0.25

ClinPred

0.85

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.54

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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