Variant 16-1999630-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001405664.1(ZNF598):c.1949C>T(p.Pro650Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00752 in 1,603,694 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0078 ( 47 hom. )

Consequence

ZNF598
NM_001405664.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.192

Variant links:

Genes affected

ZNF598 (HGNC:28079): (zinc finger protein 598, E3 ubiquitin ligase) Zinc-finger proteins bind nucleic acids and play important roles in various cellular functions, including cell proliferation, differentiation, and apoptosis. This protein and Grb10-interacting GYF protein 2 have been identified as a components of the mammalian 4EHP (m4EHP) complex. The complex is thought to function as a translation repressor in embryonic development. [provided by RefSeq, Oct 2012]

ZNF598 links:

ZNF598 (HGNC:):

ZNF598 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038484335).

BP6

Variant 16-1999630-G-A is Benign according to our data. Variant chr16-1999630-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645961.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
ZNF598	NM_001405664.1 linkuse as main transcript	c.1949C>T	p.Pro650Leu	missense_variant	11/14	NP_001392593.1
ZNF598	NM_178167.5 linkuse as main transcript	c.1919C>T	p.Pro640Leu	missense_variant	11/14	NP_835461.2	Q86UK7
ZNF598	NM_001405665.1 linkuse as main transcript	c.1901C>T	p.Pro634Leu	missense_variant	11/14	NP_001392594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF598	ENST00000562103.2 linkuse as main transcript	c.1919C>T	p.Pro640Leu	missense_variant	11/14	1		ENSP00000455308.2		H3BPG6

Frequencies

GnomAD3 genomes

AF:

0.00528

AC:

803

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00574

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00879

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00606

AC:

1417

AN:

233868

Hom.:

AF XY:

0.00607

AC XY:

785

AN XY:

129428

show subpopulations

Gnomad AFR exome

AF:

0.00121

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.000622

Gnomad EAS exome

AF:

0.0000577

Gnomad SAS exome

AF:

0.00295

Gnomad FIN exome

AF:

0.00603

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.00433

GnomAD4 exome

AF:

0.00776

AC:

11260

AN:

1451420

Hom.:

Cov.:

AF XY:

0.00754

AC XY:

5449

AN XY:

722514

show subpopulations

Gnomad4 AFR exome

AF:

0.00115

Gnomad4 AMR exome

AF:

0.00141

Gnomad4 ASJ exome

AF:

0.00100

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00275

Gnomad4 FIN exome

AF:

0.00659

Gnomad4 NFE exome

AF:

0.00925

Gnomad4 OTH exome

AF:

0.00518

GnomAD4 genome

AF:

0.00527

AC:

802

AN:

152274

Hom.:

Cov.:

AF XY:

0.00510

AC XY:

380

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.00300

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00574

Gnomad4 NFE

AF:

0.00880

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00791

Hom.:

Bravo

AF:

0.00458

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.000553

AC:

ESP6500EA

AF:

0.00576

AC:

ExAC

AF:

0.00687

AC:

821

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

ZNF598: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

2.7

DANN

Benign

0.71

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.64

.;T

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.0

N;N

Sift

Benign

0.058

T;T

Sift4G

Uncertain

0.0020

D;D

Vest4

0.056

MVP

0.35

ClinPred

0.0017

GERP RS

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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