Variant X-135349185-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000339249.5(ZNF449):c.430G>C(p.Glu144Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00015 in 1,209,609 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 48 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.00015 ( 0 hom. 45 hem. )

Consequence

ZNF449
ENST00000339249.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.80

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15404394).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF449	NM_152695.6 linkuse as main transcript	c.430G>C	p.Glu144Gln	missense_variant	3/5	ENST00000339249.5	NP_689908.3
ZNF449	XM_047441914.1 linkuse as main transcript	c.430G>C	p.Glu144Gln	missense_variant	3/5		XP_047297870.1
ZNF449	XM_017029351.2 linkuse as main transcript	c.85G>C	p.Glu29Gln	missense_variant	4/6		XP_016884840.1
ZNF449	XM_047441915.1 linkuse as main transcript	c.85G>C	p.Glu29Gln	missense_variant	4/6		XP_047297871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF449	ENST00000339249.5 linkuse as main transcript	c.430G>C	p.Glu144Gln	missense_variant	3/5	1	NM_152695.6	ENSP00000339585	P1	Q6P9G9-1

Frequencies

GnomAD3 genomes

AF:

0.0000987

AC:

AN:

111473

Hom.:

Cov.:

AF XY:

0.0000891

AC XY:

AN XY:

33673

show subpopulations

Gnomad AFR

AF:

0.0000654

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000948

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000165

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000600

AC:

AN:

183359

Hom.:

AF XY:

0.0000737

AC XY:

AN XY:

67797

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.0000855

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000155

AC:

170

AN:

1098136

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

363490

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.000190

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.0000987

AC:

AN:

111473

Hom.:

Cov.:

AF XY:

0.0000891

AC XY:

AN XY:

33673

show subpopulations

Gnomad4 AFR

AF:

0.0000654

Gnomad4 AMR

AF:

0.0000948

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000165

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000215

Hom.:

Bravo

AF:

0.000113

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Jan 23, 2024

The c.430G>C (p.E144Q) alteration is located in exon 3 (coding exon 2) of the ZNF449 gene. This alteration results from a G to C substitution at nucleotide position 430, causing the glutamic acid (E) at amino acid position 144 to be replaced by a glutamine (Q). 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

0.12

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.78

CADD

Uncertain

DANN

Uncertain

0.97

DEOGEN2

Benign

0.025

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.46

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.90

MutationTaster

Benign

0.98

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.91

REVEL

Benign

0.050

Sift

Benign

0.18

Sift4G

Benign

0.58

Polyphen

0.85

Vest4

0.081

MVP

0.58

MPC

0.79

ClinPred

0.048

GERP RS

3.6

Varity_R

0.14

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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