dbSNP rs10871453: ZNF768:p.Glu181Asp (chr16-30525597-C-A) – 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_024671.4(ZNF768):c.543G>T(p.Glu181Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 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: 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=0.09139472).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ZNF768	NM_024671.4 link	c.543G>T	p.Glu181Asp	missense_variant	Exon 2 of 2	ENST00000380412.7	NP_078947.3
ZNF768	XM_017023665.3 link	c.615G>T	p.Glu205Asp	missense_variant	Exon 2 of 2		XP_016879154.1
ZNF768	XM_017023666.2 link	c.450G>T	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>T	p.Glu181Asp	missense_variant	Exon 2 of 2	1	NM_024671.4	ENSP00000369777.5
ZNF768	ENST00000562803.1 link	c.450G>T	p.Glu150Asp	missense_variant	Exon 2 of 2	3		ENSP00000456527.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251426

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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

Cov.:

Alfa

AF:

0.0000198

Hom.:

3665

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.23

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

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.56

T;T

M_CAP

Benign

0.0064

MetaRNN

Benign

0.091

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

N;.

PhyloP100

-0.64

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.50

N;.

REVEL

Benign

0.16

Sift

Benign

0.10

T;.

Sift4G

Benign

0.60

T;T

Polyphen

0.96

D;.

Vest4

0.35

MutPred

0.076

Loss of methylation at K183 (P = 0.0996);.;

MVP

0.21

MPC

0.98

ClinPred

0.61

GERP RS

0.64

Varity_R

0.084

gMVP

0.19

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over