Genetic Variant NM_001002836.4:c.1086G>C (chr19-56088086-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001002836.4(ZNF787):c.1086G>C(p.Glu362Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,486,494 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0046 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0013 ( 5 hom. )

Consequence

ZNF787
NM_001002836.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: -3.41

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002983451).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF787	NM_001002836.4 link	c.1086G>C	p.Glu362Asp	missense_variant	Exon 3 of 3	ENST00000610935.2	NP_001002836.2	Q6DD87
ZNF787	XM_047438164.1 link	c.1086G>C	p.Glu362Asp	missense_variant	Exon 3 of 3		XP_047294120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF787	ENST00000610935.2 link	c.1086G>C	p.Glu362Asp	missense_variant	Exon 3 of 3	1	NM_001002836.4	ENSP00000478557.1		Q6DD87

Frequencies

GnomAD3 genomes

AF:

0.00455

AC:

678

AN:

148968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00435

Gnomad ASJ

AF:

0.00463

Gnomad EAS

AF:

0.00218

Gnomad SAS

AF:

0.000419

Gnomad FIN

AF:

0.0000993

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000607

Gnomad OTH

AF:

0.00493

GnomAD2 exomes

AF:

0.0000480

AC:

AN:

145912

AF XY:

0.0000357

show subpopulations

Gnomad AFR exome

AF:

0.000473

Gnomad AMR exome

AF:

0.0000473

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000117

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000293

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00126

AC:

1691

AN:

1337434

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

806

AN XY:

664818

show subpopulations

African (AFR)

AF:

0.0137

AC:

373

AN:

27316

American (AMR)

AF:

0.00435

AC:

110

AN:

25284

Ashkenazi Jewish (ASJ)

AF:

0.00443

AC:

100

AN:

22598

East Asian (EAS)

AF:

0.00194

AC:

AN:

26748

South Asian (SAS)

AF:

0.000457

AC:

AN:

76524

European-Finnish (FIN)

AF:

0.000183

AC:

AN:

38270

Middle Eastern (MID)

AF:

0.00514

AC:

AN:

3892

European-Non Finnish (NFE)

AF:

0.000821

AC:

872

AN:

1062446

Other (OTH)

AF:

0.00224

AC:

122

AN:

54356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

105

209

314

418

523

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.00456

AC:

680

AN:

149060

Hom.:

Cov.:

AF XY:

0.00434

AC XY:

315

AN XY:

72658

show subpopulations

African (AFR)

AF:

0.0131

AC:

538

AN:

41156

American (AMR)

AF:

0.00435

AC:

AN:

14262

Ashkenazi Jewish (ASJ)

AF:

0.00463

AC:

AN:

3456

East Asian (EAS)

AF:

0.00219

AC:

AN:

4570

South Asian (SAS)

AF:

0.000420

AC:

AN:

4762

European-Finnish (FIN)

AF:

0.0000993

AC:

AN:

10066

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000607

AC:

AN:

67536

Other (OTH)

AF:

0.00488

AC:

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

102

136

170

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:

0.000858

Hom.:

ExAC

AF:

0.0000439

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Oromandibular-limb hypogenesis spectrum

Uncertain:1

Aug 12, 2016

CHU Sainte-Justine Research Center, University of Montreal

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.0040

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.011

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0091

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0030

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

PhyloP100

-3.4

PrimateAI

Pathogenic

0.87

Sift4G

Benign

0.23

Polyphen

0.0

Vest4

0.063

MutPred

0.36

Gain of helix (P = 0.062);

MVP

0.043

ClinPred

0.0094

GERP RS

0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.034

gMVP

0.034

Mutation Taster

=97/3

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

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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