Genetic Variant ZNF764:p.Lys340Glu (chr16-30555400-T-C) – 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_001172679.2(ZNF764):c.1018A>G(p.Lys340Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,567,006 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

ZNF764
NM_001172679.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.606

Publications

0 publications found

Variant links:

Genes affected

ZNF764 (HGNC:28200): (zinc finger protein 764) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF764 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=0.1434913).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172679.2. 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
	ZNF764	NM_001172679.2	MANE Select	c.1018A>G	p.Lys340Glu	missense	Exon 3 of 3	NP_001166150.1	Q96H86-2
	ZNF764	NM_033410.4		c.1021A>G	p.Lys341Glu	missense	Exon 3 of 3	NP_219363.2	Q96H86-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF764	ENST00000395091.3	TSL:2 MANE Select	c.1018A>G	p.Lys340Glu	missense	Exon 3 of 3	ENSP00000378526.2	Q96H86-2
ZNF764	ENST00000252797.6	TSL:1	c.1021A>G	p.Lys341Glu	missense	Exon 3 of 3	ENSP00000252797.2	Q96H86-1
ZNF764	ENST00000952475.1		c.904A>G	p.Lys302Glu	missense	Exon 2 of 2	ENSP00000622534.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152198

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

195234

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000283

AC:

AN:

1414808

Hom.:

Cov.:

AF XY:

0.0000199

AC XY:

AN XY:

701826

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32284

American (AMR)

AF:

0.00

AC:

AN:

39224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25024

East Asian (EAS)

AF:

0.00

AC:

AN:

38108

South Asian (SAS)

AF:

0.00

AC:

AN:

82230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5600

European-Non Finnish (NFE)

AF:

0.0000369

AC:

AN:

1084482

Other (OTH)

AF:

0.00

AC:

AN:

58518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

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:

0.0000197

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

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:

0.0000712

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000168

AC:

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

Pathogenic

0.93

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.029

M_CAP

Benign

0.017

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.3

PhyloP100

0.61

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.11

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0090

Polyphen

0.40

Vest4

0.33

MutPred

0.35

Loss of methylation at K341 (P = 2e-04)

MVP

0.41

MPC

0.33

ClinPred

0.85

GERP RS

4.1

Varity_R

0.38

gMVP

0.18

Mutation Taster

=96/4

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