Variant 18-14105437-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_145287.4(ZNF519):c.1103G>T(p.Arg368Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000205 in 1,613,566 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 2 hom. )

Consequence

ZNF519
NM_145287.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.499

Variant links:

Genes affected

ZNF519 (HGNC:30574): (zinc finger protein 519) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and chromatin 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]

ZNF519 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.087585986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF519	NM_145287.4 linkuse as main transcript	c.1103G>T	p.Arg368Ile	missense_variant	3/3	ENST00000590202.3
ZNF519	NR_033354.2 linkuse as main transcript	n.162-20361G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF519	ENST00000590202.3 linkuse as main transcript	c.1103G>T	p.Arg368Ile	missense_variant	3/3	1	NM_145287.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

151900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000116

AC:

AN:

250772

Hom.:

AF XY:

0.000148

AC XY:

AN XY:

135538

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000211

AC:

308

AN:

1461666

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

138

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000244

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000145

AC:

AN:

151900

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000148

Hom.:

Bravo

AF:

0.000125

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

The c.1103G>T (p.R368I) alteration is located in exon 3 (coding exon 3) of the ZNF519 gene. This alteration results from a G to T substitution at nucleotide position 1103, causing the arginine (R) at amino acid position 368 to be replaced by an isoleucine (I). 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

0.31

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.59

Cadd

Benign

Dann

Benign

0.94

DEOGEN2

Benign

0.043

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.35

M_CAP

Benign

0.0049

MetaRNN

Benign

0.088

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

0.69

D;D

PrimateAI

Benign

0.44

Sift4G

Benign

0.12

Polyphen

0.89

Vest4

0.15

MVP

0.33

MPC

0.016

ClinPred

0.045

GERP RS

-0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.13

gMVP

0.029

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