dbSNP rs685688: ZNF492:p.Glu229Asp (chr19-22664356-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020855.3(ZNF492):c.687G>C(p.Glu229Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000373 in 1,393,838 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000037 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

ZNF492
NM_020855.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -6.21

Publications

0 publications found

Variant links:

Genes affected

ZNF492 (HGNC:23707): (zinc finger protein 492) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF492 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.036066175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF492	NM_020855.3 link	c.687G>C	p.Glu229Asp	missense_variant	Exon 4 of 4	ENST00000456783.3	NP_065906.1	Q9P255
ZNF492	XM_047439130.1 link	c.687G>C	p.Glu229Asp	missense_variant	Exon 4 of 4		XP_047295086.1
ZNF492	XM_047439131.1 link	c.591G>C	p.Glu197Asp	missense_variant	Exon 3 of 3		XP_047295087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF492	ENST00000456783.3 link	c.687G>C	p.Glu229Asp	missense_variant	Exon 4 of 4	1	NM_020855.3	ENSP00000413660.2		Q9P255

Frequencies

GnomAD3 genomes

AF:

0.0000338

AC:

AN:

147946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000752

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000222

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000760

AC:

AN:

105262

AF XY:

0.000128

show subpopulations

Gnomad AFR exome

AF:

0.000153

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000238

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000373

AC:

AN:

1393838

Hom.:

Cov.:

AF XY:

0.0000465

AC XY:

AN XY:

688142

show subpopulations

African (AFR)

AF:

0.0000320

AC:

AN:

31250

American (AMR)

AF:

0.00

AC:

AN:

34448

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24178

East Asian (EAS)

AF:

0.0000544

AC:

AN:

36740

South Asian (SAS)

AF:

0.000479

AC:

AN:

79256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50004

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4064

European-Non Finnish (NFE)

AF:

0.00000836

AC:

AN:

1076432

Other (OTH)

AF:

0.0000348

AC:

AN:

57466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000338

AC:

AN:

148072

Hom.:

Cov.:

AF XY:

0.0000415

AC XY:

AN XY:

72226

show subpopulations

African (AFR)

AF:

0.0000749

AC:

AN:

40038

American (AMR)

AF:

0.00

AC:

AN:

14756

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3426

East Asian (EAS)

AF:

0.00

AC:

AN:

4974

South Asian (SAS)

AF:

0.000222

AC:

AN:

4508

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

66886

Other (OTH)

AF:

0.00

AC:

AN:

2006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

ExAC

AF:

0.0000306

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 02, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.687G>C (p.E229D) alteration is located in exon 4 (coding exon 3) of the ZNF492 gene. This alteration results from a G to C substitution at nucleotide position 687, causing the glutamic acid (E) at amino acid position 229 to be replaced by an aspartic acid (D). 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

0.15

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.20

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.016

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0047

LIST_S2

Benign

0.014

M_CAP

Benign

0.00067

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.90

PhyloP100

-6.2

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.0040

Sift

Benign

0.095

Sift4G

Benign

0.13

Polyphen

0.0010

Vest4

0.063

MutPred

0.42

Loss of disorder (P = 0.0862);

MVP

0.14

MPC

1.1

ClinPred

0.028

GERP RS

-2.6

Varity_R

0.061

gMVP

0.010

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over