Variant 16-1999659-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001405664.1(ZNF598):c.1920C>T(p.Ala640Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 1,608,328 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0035 ( 16 hom. )

Consequence

ZNF598
NM_001405664.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.39

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 16-1999659-G-A is Benign according to our data. Variant chr16-1999659-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645962.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.39 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
ZNF598	NM_001405664.1 linkuse as main transcript	c.1920C>T	p.Ala640Ala	synonymous_variant	11/14	NP_001392593.1
ZNF598	NM_178167.5 linkuse as main transcript	c.1890C>T	p.Ala630Ala	synonymous_variant	11/14	NP_835461.2	Q86UK7
ZNF598	NM_001405665.1 linkuse as main transcript	c.1872C>T	p.Ala624Ala	synonymous_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.1890C>T	p.Ala630Ala	synonymous_variant	11/14	1		ENSP00000455308.2		H3BPG6

Frequencies

GnomAD3 genomes

AF:

0.00290

AC:

442

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00537

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00310

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00358

AC:

855

AN:

238906

Hom.:

AF XY:

0.00383

AC XY:

504

AN XY:

131726

show subpopulations

Gnomad AFR exome

AF:

0.000632

Gnomad AMR exome

AF:

0.000972

Gnomad ASJ exome

AF:

0.0250

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00141

Gnomad FIN exome

AF:

0.00369

Gnomad NFE exome

AF:

0.00397

Gnomad OTH exome

AF:

0.00442

GnomAD4 exome

AF:

0.00351

AC:

5118

AN:

1456048

Hom.:

Cov.:

AF XY:

0.00356

AC XY:

2577

AN XY:

724588

show subpopulations

Gnomad4 AFR exome

AF:

0.000509

Gnomad4 AMR exome

AF:

0.00135

Gnomad4 ASJ exome

AF:

0.0261

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00169

Gnomad4 FIN exome

AF:

0.00385

Gnomad4 NFE exome

AF:

0.00332

Gnomad4 OTH exome

AF:

0.00554

GnomAD4 genome

AF:

0.00290

AC:

442

AN:

152280

Hom.:

Cov.:

AF XY:

0.00287

AC XY:

214

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00418

Gnomad4 ASJ

AF:

0.0202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00537

Gnomad4 NFE

AF:

0.00310

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00478

Hom.:

Bravo

AF:

0.00290

EpiCase

AF:

0.00360

EpiControl

AF:

0.00392

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

Dec 01, 2022

ZNF598: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.31

DANN

Benign

0.58

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