Variant 15-64674331-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015042.2(ZNF609):c.1477G>A(p.Val493Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000339 in 1,613,960 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 1 hom. )

Consequence

ZNF609
NM_015042.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.52

Variant links:

Genes affected

ZNF609 (HGNC:29003): (zinc finger protein 609) Predicted to enable promoter-specific chromatin binding activity. Involved in regulation of myoblast proliferation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF609 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013904095).

BS2

High AC in GnomAd4 at 59 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF609	NM_015042.2 linkuse as main transcript	c.1477G>A	p.Val493Ile	missense_variant	5/10	ENST00000326648.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF609	ENST00000326648.5 linkuse as main transcript	c.1477G>A	p.Val493Ile	missense_variant	5/10	5	NM_015042.2	P1	O15014-1
ZNF609	ENST00000559364.1 linkuse as main transcript	n.881G>A		non_coding_transcript_exon_variant	4/4	1

Frequencies

GnomAD3 genomes

AF:

0.000382

AC:

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.0000946

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000434

AC:

109

AN:

251358

Hom.:

AF XY:

0.000500

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.00114

Gnomad SAS exome

AF:

0.000882

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000334

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000334

AC:

488

AN:

1461882

Hom.:

Cov.:

AF XY:

0.000367

AC XY:

267

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00214

Gnomad4 EAS exome

AF:

0.00146

Gnomad4 SAS exome

AF:

0.000649

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000260

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000388

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.000525

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.000832

Gnomad4 FIN

AF:

0.0000946

Gnomad4 NFE

AF:

0.000427

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000513

Hom.:

Bravo

AF:

0.000321

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000453

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000296

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

May 21, 2024

The c.1477G>A (p.V493I) alteration is located in exon 4 (coding exon 4) of the ZNF609 gene. This alteration results from a G to A substitution at nucleotide position 1477, causing the valine (V) at amino acid position 493 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

0.073

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.064

Eigen

Benign

0.0065

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0024

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.29

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.65

REVEL

Benign

0.028

Sift

Benign

0.13

Sift4G

Benign

0.25

Polyphen

0.0030

Vest4

0.16

MVP

0.043

MPC

0.23

ClinPred

0.017

GERP RS

5.6

Varity_R

0.028

gMVP

0.32

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