Genetic Variant ZNF787:p.Ala254Thr (chr19-56088412-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001002836.4(ZNF787):c.760G>A(p.Ala254Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,129,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ZNF787
NM_001002836.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.257

Publications

0 publications found

Variant links:

Genes affected

ZNF787 (HGNC:26998): (zinc finger protein 787) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF787 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.100099504).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002836.4. 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
	ZNF787	NM_001002836.4	MANE Select	c.760G>A	p.Ala254Thr	missense	Exon 3 of 3	NP_001002836.2	Q6DD87

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF787	ENST00000610935.2	TSL:1 MANE Select	c.760G>A	p.Ala254Thr	missense	Exon 3 of 3	ENSP00000478557.1	Q6DD87
ZNF787	ENST00000969467.1		c.760G>A	p.Ala254Thr	missense	Exon 3 of 3	ENSP00000639526.1
ZNF787	ENST00000969468.1		c.760G>A	p.Ala254Thr	missense	Exon 4 of 4	ENSP00000639527.1

Frequencies

GnomAD3 genomes

AF:

0.00000685

AC:

AN:

145976

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:

0.0000152

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000183

AC:

AN:

984022

Hom.:

Cov.:

AF XY:

0.0000237

AC XY:

AN XY:

463394

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19020

American (AMR)

AF:

0.00

AC:

AN:

5214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9676

East Asian (EAS)

AF:

0.00

AC:

AN:

16056

South Asian (SAS)

AF:

0.00

AC:

AN:

19620

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17900

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2366

European-Non Finnish (NFE)

AF:

0.0000210

AC:

AN:

857846

Other (OTH)

AF:

0.00

AC:

AN:

36324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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

AF:

0.00000685

AC:

AN:

145976

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71058

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40482

American (AMR)

AF:

0.00

AC:

AN:

14736

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3390

East Asian (EAS)

AF:

0.00

AC:

AN:

4946

South Asian (SAS)

AF:

0.00

AC:

AN:

4782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8536

Middle Eastern (MID)

AF:

0.00

AC:

AN:

296

European-Non Finnish (NFE)

AF:

0.0000152

AC:

AN:

65898

Other (OTH)

AF:

0.00

AC:

AN:

2014

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

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

Benign

0.12

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0074

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.46

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.55

PhyloP100

0.26

PrimateAI

Pathogenic

0.85

Sift4G

Benign

0.53

Polyphen

0.58

Vest4

0.21

MutPred

0.26

Gain of glycosylation at A254 (P = 0.0024)

MVP

0.043

ClinPred

0.082

GERP RS

1.4

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.2

Varity_R

0.016

gMVP

0.22

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over