Variant 15-64622888-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015042.2(ZNF609):c.809A>T(p.Asn270Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

ZNF609
NM_015042.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.56

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:

LOC101930091 (HGNC:):

LOC101930091 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=0.1526309).

BS2

High AC in GnomAdExome4 at 32 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF609	NM_015042.2 linkuse as main transcript	c.809A>T	p.Asn270Ile	missense_variant	3/10	ENST00000326648.5	NP_055857.1
LOC101930091	XR_007064678.1 linkuse as main transcript	n.255+3373T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF609	ENST00000326648.5 linkuse as main transcript	c.809A>T	p.Asn270Ile	missense_variant	3/10	5	NM_015042.2	ENSP00000316527	P1	O15014-1
ZNF609	ENST00000558680.5 linkuse as main transcript	n.166A>T		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251432

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

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

Feb 21, 2024

The c.809A>T (p.N270I) alteration is located in exon 2 (coding exon 2) of the ZNF609 gene. This alteration results from a A to T substitution at nucleotide position 809, causing the asparagine (N) at amino acid position 270 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

0.27

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.27

Eigen

Benign

-0.068

Eigen_PC

Benign

-0.023

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.020

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.052

Sift

Uncertain

0.0040

Sift4G

Benign

0.088

Polyphen

0.57

Vest4

0.42

MutPred

0.32

Loss of loop (P = 0.0288);

MVP

0.068

MPC

0.35

ClinPred

0.66

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.60

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