Variant 19-44386725-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_152354.6(ZNF285):c.1520T>C(p.Ile507Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000927 in 1,614,042 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00094 ( 1 hom. )

Consequence

ZNF285
NM_152354.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.15

Variant links:

Genes affected

ZNF285 (HGNC:13079): (zinc finger protein 285) 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]

ZNF285 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009248853).

BP6

Variant 19-44386725-A-G is Benign according to our data. Variant chr19-44386725-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2341503.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF285	NM_152354.6 linkuse as main transcript	c.1520T>C	p.Ile507Thr	missense_variant	4/4	ENST00000614994.5	NP_689567.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF285	ENST00000614994.5 linkuse as main transcript	c.1520T>C	p.Ile507Thr	missense_variant	4/4	1	NM_152354.6	ENSP00000483662	P2	Q96NJ3-1
ZNF285	ENST00000591679.5 linkuse as main transcript	c.1541T>C	p.Ile514Thr	missense_variant	5/5	4		ENSP00000464788	A2
ZNF285	ENST00000544719.6 linkuse as main transcript	c.1520T>C	p.Ile507Thr	missense_variant	4/4	5		ENSP00000439431	P2	Q96NJ3-1

Frequencies

GnomAD3 genomes

AF:

0.000802

AC:

122

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000617

AC:

155

AN:

251128

Hom.:

AF XY:

0.000619

AC XY:

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.000695

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000951

Gnomad OTH exome

AF:

0.000981

GnomAD4 exome

AF:

0.000940

AC:

1374

AN:

1461800

Hom.:

Cov.:

AF XY:

0.000892

AC XY:

649

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000649

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00114

Gnomad4 OTH exome

AF:

0.000778

GnomAD4 genome

AF:

0.000801

AC:

122

AN:

152242

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000875

Hom.:

Bravo

AF:

0.000748

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000519

AC:

EpiCase

AF:

0.000982

EpiControl

AF:

0.00107

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.5

DANN

Benign

0.28

Eigen

Benign

-2.0

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.025

.;.;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.0092

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;N;N;N

REVEL

Benign

0.057

Sift4G

Benign

1.0

T;T;T

Vest4

0.036

MVP

0.10

ClinPred

0.0011

GERP RS

-1.6

gMVP

0.0068

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