Variant 19-12464664-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_152601.4(ZNF709):c.1258C>T(p.His420Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 87,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF709
NM_152601.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.102

Variant links:

Genes affected

ZNF709 (HGNC:20629): (zinc finger protein 709) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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]

ZNF709 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012298375).

BP6

Variant 19-12464664-G-A is Benign according to our data. Variant chr19-12464664-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2210358.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF709	NM_152601.4 linkuse as main transcript	c.1258C>T	p.His420Tyr	missense_variant	4/4	ENST00000397732.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF709	ENST00000397732.8 linkuse as main transcript	c.1258C>T	p.His420Tyr	missense_variant	4/4	1	NM_152601.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00195

AC:

171

AN:

87618

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00240

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00120

Gnomad ASJ

AF:

0.00331

Gnomad EAS

AF:

0.00260

Gnomad SAS

AF:

0.00221

Gnomad FIN

AF:

0.000812

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00199

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00164

AC:

2168

AN:

1323386

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

1122

AN XY:

654958

show subpopulations

Gnomad4 AFR exome

AF:

0.00253

Gnomad4 AMR exome

AF:

0.00691

Gnomad4 ASJ exome

AF:

0.00188

Gnomad4 EAS exome

AF:

0.00405

Gnomad4 SAS exome

AF:

0.00546

Gnomad4 FIN exome

AF:

0.000903

Gnomad4 NFE exome

AF:

0.00114

Gnomad4 OTH exome

AF:

0.00191

GnomAD4 genome

AF:

0.00195

AC:

171

AN:

87700

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

AN XY:

43598

show subpopulations

Gnomad4 AFR

AF:

0.00239

Gnomad4 AMR

AF:

0.00120

Gnomad4 ASJ

AF:

0.00331

Gnomad4 EAS

AF:

0.00260

Gnomad4 SAS

AF:

0.00222

Gnomad4 FIN

AF:

0.000812

Gnomad4 NFE

AF:

0.00199

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0229

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

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

Dec 27, 2022

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

0.067

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.051

DANN

Benign

0.85

DEOGEN2

Benign

0.024

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0083

LIST_S2

Benign

0.082

T;.

M_CAP

Benign

0.00098

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.4

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

3.9

N;N

REVEL

Benign

0.089

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0020

B;.

Vest4

0.11

MVP

0.13

MPC

0.39

ClinPred

0.00056

GERP RS

0.070

Varity_R

0.035

gMVP

0.024

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