Genetic Variant ZNF768:p.Glu181Asp (chr16-30525597-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024671.4(ZNF768):c.543G>C(p.Glu181Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,614,046 control chromosomes in the GnomAD database, including 113,212 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 11398 hom., cov: 33)

Exomes 𝑓: 0.36 ( 101814 hom. )

Consequence

ZNF768
NM_024671.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.638

Publications

32 publications found

Variant links:

Genes affected

ZNF768 (HGNC:26273): (zinc finger protein 768) Enables RNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF768 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0010181665).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ZNF768	NM_024671.4 link	c.543G>C	p.Glu181Asp	missense_variant	Exon 2 of 2	ENST00000380412.7	NP_078947.3
ZNF768	XM_017023665.3 link	c.615G>C	p.Glu205Asp	missense_variant	Exon 2 of 2		XP_016879154.1
ZNF768	XM_017023666.2 link	c.450G>C	p.Glu150Asp	missense_variant	Exon 2 of 2		XP_016879155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF768	ENST00000380412.7 link	c.543G>C	p.Glu181Asp	missense_variant	Exon 2 of 2	1	NM_024671.4	ENSP00000369777.5
ZNF768	ENST00000562803.1 link	c.450G>C	p.Glu150Asp	missense_variant	Exon 2 of 2	3		ENSP00000456527.1

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56443

AN:

152068

Hom.:

11399

Cov.:

show subpopulations

Gnomad AFR

AF:

0.476

Gnomad AMI

AF:

0.437

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.00519

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.389

Gnomad OTH

AF:

0.336

GnomAD2 exomes

AF:

0.293

AC:

73743

AN:

251426

AF XY:

0.292

show subpopulations

Gnomad AFR exome

AF:

0.477

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.330

Gnomad EAS exome

AF:

0.00348

Gnomad FIN exome

AF:

0.261

Gnomad NFE exome

AF:

0.377

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.361

AC:

527162

AN:

1461860

Hom.:

101814

Cov.:

AF XY:

0.355

AC XY:

258286

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.482

AC:

16154

AN:

33480

American (AMR)

AF:

0.202

AC:

9046

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.320

AC:

8351

AN:

26132

East Asian (EAS)

AF:

0.00189

AC:

AN:

39700

South Asian (SAS)

AF:

0.186

AC:

16012

AN:

86254

European-Finnish (FIN)

AF:

0.257

AC:

13738

AN:

53414

Middle Eastern (MID)

AF:

0.313

AC:

1802

AN:

5766

European-Non Finnish (NFE)

AF:

0.397

AC:

441202

AN:

1111996

Other (OTH)

AF:

0.344

AC:

20782

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

23064

46128

69191

92255

115319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13506

27012

40518

54024

67530

<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:

0.371

AC:

56458

AN:

152186

Hom.:

11398

Cov.:

AF XY:

0.359

AC XY:

26746

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.475

AC:

19701

AN:

41498

American (AMR)

AF:

0.285

AC:

4360

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

1168

AN:

3470

East Asian (EAS)

AF:

0.00520

AC:

AN:

5192

South Asian (SAS)

AF:

0.157

AC:

757

AN:

4832

European-Finnish (FIN)

AF:

0.267

AC:

2835

AN:

10602

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.389

AC:

26421

AN:

67982

Other (OTH)

AF:

0.333

AC:

703

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1799

3598

5396

7195

8994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

518

1036

1554

2072

2590

<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:

0.375

Hom.:

3665

Bravo

AF:

0.378

TwinsUK

AF:

0.407

AC:

1510

ESP6500AA

AF:

0.461

AC:

2024

ESP6500EA

AF:

0.389

AC:

3348

ExAC

AF:

0.299

AC:

36357

Asia WGS

AF:

0.118

AC:

411

AN:

3478

EpiCase

AF:

0.374

EpiControl

AF:

0.380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0088

T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.21

LIST_S2

Benign

0.56

T;T

MetaRNN

Benign

0.0010

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

N;.

PhyloP100

-0.64

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.50

N;.

Sift

Benign

0.10

T;.

Sift4G

Benign

0.60

T;T

Vest4

0.35

ClinPred

0.017

GERP RS

0.64

Varity_R

0.084

gMVP

0.19

Mutation Taster

=96/4

polymorphism (auto)

(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

Computational scores

Splicing

Publications

Other links and lift over