dbSNP rs1004073176: ZNF768:p.Arg540His (chr16-30524521-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_024671.4(ZNF768):c.1619G>A(p.Arg540His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000872 in 1,605,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

ZNF768
NM_024671.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38

Publications

0 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:

Genome browser will be placed here

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=0.17019135).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024671.4. 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
	ZNF768	NM_024671.4	MANE Select	c.1619G>A	p.Arg540His	missense	Exon 2 of 2	NP_078947.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF768	ENST00000380412.7	TSL:1 MANE Select	c.1619G>A	p.Arg540His	missense	Exon 2 of 2	ENSP00000369777.5	Q9H5H4
	ZNF768	ENST00000562803.1	TSL:3	c.1526G>A	p.Arg509His	missense	Exon 2 of 2	ENSP00000456527.1	H3BS42

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000124

AC:

AN:

241728

AF XY:

0.0000152

show subpopulations

Gnomad AFR exome

AF:

0.000132

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:

0.00000911

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000688

AC:

AN:

1452916

Hom.:

Cov.:

AF XY:

0.00000830

AC XY:

AN XY:

722706

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33394

American (AMR)

AF:

0.00

AC:

AN:

44524

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25856

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.00

AC:

AN:

85638

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49458

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4462

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1109866

Other (OTH)

AF:

0.0000166

AC:

AN:

60062

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

AF:

0.0000263

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41472

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68050

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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.:

Bravo

AF:

0.0000264

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

0.22

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.036

Eigen

Benign

0.043

Eigen_PC

Benign

0.042

FATHMM_MKL

Benign

0.25

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.014

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

1.4

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.96

REVEL

Benign

0.10

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.40

MutPred

0.48

Loss of methylation at R540 (P = 0.0157)

MVP

0.27

MPC

1.9

ClinPred

0.49

GERP RS

5.5

Varity_R

0.20

gMVP

0.69

Mutation Taster

=88/12

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over