Genetic Variant ZNF284:p.His169Tyr (chr19-44085983-C-T) – 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.505C>T(p.His169Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000131 in 1,614,108 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 0.00070 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

ZNF284
NM_001037813.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.61

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 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=0.007915169).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF284	NM_001037813.4 link	c.505C>T	p.His169Tyr	missense_variant	Exon 5 of 5	ENST00000421176.4	NP_001032902.1	Q2VY69
ZNF284	XM_011526907.4 link	c.505C>T	p.His169Tyr	missense_variant	Exon 5 of 5		XP_011525209.1	Q2VY69
ZNF284	XM_011526908.4 link	c.505C>T	p.His169Tyr	missense_variant	Exon 6 of 6		XP_011525210.1	Q2VY69
ZNF284	XM_024451486.2 link	c.505C>T	p.His169Tyr	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.505C>T	p.His169Tyr	missense_variant	Exon 5 of 5	1	NM_001037813.4	ENSP00000411032.2	Q2VY69
ENSG00000267022	ENST00000591793.1 link	n.*551C>T		non_coding_transcript_exon_variant	Exon 11 of 11	2		ENSP00000467018.1	K7ENM7
ENSG00000267022	ENST00000591793.1 link	n.*551C>T		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000467018.1	K7ENM7

Frequencies

GnomAD3 genomes

AF:

0.000703

AC:

107

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000209

AC:

AN:

249324

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135244

show subpopulations

Gnomad AFR exome

AF:

0.00285

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000718

AC:

105

AN:

1461762

Hom.:

Cov.:

AF XY:

0.0000660

AC XY:

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.00227

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000702

AC:

107

AN:

152346

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00241

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000144

Hom.:

Bravo

AF:

0.000808

ESP6500AA

AF:

0.00146

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.505C>T (p.H169Y) alteration is located in exon 5 (coding exon 4) of the ZNF284 gene. This alteration results from a C to T substitution at nucleotide position 505, causing the histidine (H) at amino acid position 169 to be replaced by a tyrosine (Y). 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

0.11

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.2

DANN

Benign

0.75

DEOGEN2

Benign

0.086

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.079

M_CAP

Benign

0.0022

MetaRNN

Benign

0.0079

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.093

Sift

Benign

0.36

Sift4G

Benign

0.072

Polyphen

0.0

Vest4

0.24

MVP

0.38

MPC

0.034

ClinPred

0.042

GERP RS

1.5

Varity_R

0.067

gMVP

0.0072

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

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