Genetic Variant NM_152695.6:c.1390A>G (chrX-135360909-A-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_152695.6(ZNF449):c.1390A>G(p.Lys464Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,209,540 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. 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 0.000018 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000011 ( 0 hom. 4 hem. )

Consequence

ZNF449
NM_152695.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.323

Publications

0 publications found

Variant links:

Genes affected

ZNF449 (HGNC:21039): (zinc finger protein 449) This gene encodes a nuclear protein that likely functions as a transcription factor. The protein includes an N-terminal SCAN domain, and seven C2H2-type zinc finger motifs. [provided by RefSeq, May 2010]

ZNF449 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3187411).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152695.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF449	NM_152695.6	MANE Select	c.1390A>G	p.Lys464Glu	missense	Exon 5 of 5	NP_689908.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF449	ENST00000339249.5	TSL:1 MANE Select	c.1390A>G	p.Lys464Glu	missense	Exon 5 of 5	ENSP00000339585.4	Q6P9G9-1
ZNF449	ENST00000850984.1		c.1390A>G	p.Lys464Glu	missense	Exon 5 of 5	ENSP00000521066.1
ZNF449	ENST00000887114.1		c.1390A>G	p.Lys464Glu	missense	Exon 5 of 5	ENSP00000557173.1

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111782

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000377

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000220

AC:

AN:

182146

AF XY:

0.0000150

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000491

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1097758

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

363202

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26389

American (AMR)

AF:

0.00

AC:

AN:

35142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19340

East Asian (EAS)

AF:

0.00

AC:

AN:

30201

South Asian (SAS)

AF:

0.00

AC:

AN:

54016

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40517

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.0000143

AC:

AN:

841945

Other (OTH)

AF:

0.00

AC:

AN:

46074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111782

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

33976

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30758

American (AMR)

AF:

0.00

AC:

AN:

10546

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2640

East Asian (EAS)

AF:

0.00

AC:

AN:

3585

South Asian (SAS)

AF:

0.00

AC:

AN:

2703

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6061

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000377

AC:

AN:

53073

Other (OTH)

AF:

0.00

AC:

AN:

1494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000113

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.66

M_CAP

Benign

0.058

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.79

MutationAssessor

Benign

-0.15

PhyloP100

0.32

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.5

REVEL

Benign

0.24

Sift

Benign

0.12

Sift4G

Benign

0.85

Polyphen

0.96

Vest4

0.19

MutPred

0.46

Loss of methylation at K464 (P = 0)

MVP

0.85

MPC

0.99

ClinPred

0.59

GERP RS

4.2

Varity_R

0.32

gMVP

0.19

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over