Genetic Variant ZNF772:p.Glu341Lys (chr19-57473600-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001144068.2(ZNF772):c.1021G>A(p.Glu341Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,613,976 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00084 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

ZNF772
NM_001144068.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0390

Publications

4 publications found

Variant links:

Genes affected

ZNF772 (HGNC:33106): (zinc finger protein 772) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific 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]

ZNF772 links:

ENSG00000268163 (HGNC:):

ENSG00000268163 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03127113).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144068.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF772	NM_001144068.2	MANE Select	c.1021G>A	p.Glu341Lys	missense	Exon 4 of 4	NP_001137540.1	Q68DY9-3
ZNF772	NM_001024596.3		c.1144G>A	p.Glu382Lys	missense	Exon 5 of 5	NP_001019767.1	Q68DY9-1
ZNF772	NM_001439216.1		c.982G>A	p.Glu328Lys	missense	Exon 3 of 3	NP_001426145.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF772	ENST00000356584.8	TSL:2 MANE Select	c.1021G>A	p.Glu341Lys	missense	Exon 4 of 4	ENSP00000348992.3	Q68DY9-3
ZNF772	ENST00000343280.8	TSL:1	c.1144G>A	p.Glu382Lys	missense	Exon 5 of 5	ENSP00000341165.4	Q68DY9-1
ZNF772	ENST00000427512.6	TSL:1	c.808G>A	p.Glu270Lys	missense	Exon 2 of 2	ENSP00000395967.2	Q68DY9-2

Frequencies

GnomAD3 genomes

AF:

0.000842

AC:

128

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000912

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000680

AC:

171

AN:

251460

AF XY:

0.000773

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000958

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.00113

AC:

1650

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

813

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33480

American (AMR)

AF:

0.00132

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39698

South Asian (SAS)

AF:

0.000243

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.000318

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00135

AC:

1497

AN:

1111998

Other (OTH)

AF:

0.000729

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

101

203

304

406

507

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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:

0.000842

AC:

128

AN:

152108

Hom.:

Cov.:

AF XY:

0.000955

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41490

American (AMR)

AF:

0.00321

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000387

AC:

AN:

5172

South Asian (SAS)

AF:

0.000208

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000912

AC:

AN:

67988

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000936

Hom.:

Bravo

AF:

0.000997

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000659

AC:

EpiCase

AF:

0.00120

EpiControl

AF:

0.00154

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

0.26

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.095

Eigen

Benign

0.069

Eigen_PC

Benign

0.0058

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.25

M_CAP

Benign

0.0041

MetaRNN

Benign

0.031

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.035

PhyloP100

0.039

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.16

Sift

Benign

0.098

Sift4G

Uncertain

0.015

Polyphen

1.0

Vest4

0.26

MVP

0.45

MPC

0.86

ClinPred

0.054

GERP RS

4.1

Varity_R

0.32

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