Variant chr19-52765737-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001321866.4(ZNF600):c.2226G>C(p.Lys742Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00722 in 1,613,840 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0074 ( 57 hom. )

Consequence

ZNF600
NM_001321866.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.469

Variant links:

Genes affected

ZNF600 (HGNC:30951): (zinc finger protein 600) Predicted to enable DNA-binding transcription activator 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]

ZNF600 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008238077).

BP6

Variant 19-52765737-C-G is Benign according to our data. Variant chr19-52765737-C-G is described in ClinVar as [Benign]. Clinvar id is 773777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF600	NM_001321866.4 linkuse as main transcript	c.2226G>C	p.Lys742Asn	missense_variant	6/6	ENST00000692063.1	NP_001308795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF600	ENST00000692063.1 linkuse as main transcript	c.2226G>C	p.Lys742Asn	missense_variant	6/6		NM_001321866.4	ENSP00000509267	P1

Frequencies

GnomAD3 genomes

AF:

0.00594

AC:

903

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.00894

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00510

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00969

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00604

AC:

1516

AN:

251144

Hom.:

AF XY:

0.00610

AC XY:

828

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00364

Gnomad ASJ exome

AF:

0.00813

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.00628

Gnomad NFE exome

AF:

0.00961

Gnomad OTH exome

AF:

0.00734

GnomAD4 exome

AF:

0.00735

AC:

10744

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00720

AC XY:

5238

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00389

Gnomad4 ASJ exome

AF:

0.00654

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000452

Gnomad4 FIN exome

AF:

0.00719

Gnomad4 NFE exome

AF:

0.00862

Gnomad4 OTH exome

AF:

0.00566

GnomAD4 genome

AF:

0.00593

AC:

903

AN:

152180

Hom.:

Cov.:

AF XY:

0.00571

AC XY:

425

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.00536

Gnomad4 ASJ

AF:

0.00894

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00510

Gnomad4 NFE

AF:

0.00969

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00901

Hom.:

Bravo

AF:

0.00572

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0101

AC:

ExAC

AF:

0.00626

AC:

760

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.83

T;T

MetaRNN

Benign

0.0082

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.6

D;.

REVEL

Benign

0.037

Sift

Uncertain

0.015

D;.

Sift4G

Pathogenic

0.0010

D;.

Polyphen

1.0

D;.

Vest4

0.14

MutPred

0.53

Loss of methylation at K673 (P = 0.0056);.;

MVP

0.44

MPC

0.25

ClinPred

0.051

GERP RS

0.57

Varity_R

0.10

gMVP

0.011

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