Genetic Variant ZNF112:p.Arg762Gln (chr19-44327872-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_013380.4(ZNF112):c.2285G>A(p.Arg762Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,613,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R762W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ZNF112
NM_013380.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.29

Publications

0 publications found

Variant links:

Genes affected

ZNF112 (HGNC:12892): (zinc finger protein 112) Predicted to enable DNA-binding transcription activator 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]

ZNF112 Gene-Disease associations (from GenCC):

Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ZNF112 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038942814).

BP6

Variant 19-44327872-C-T is Benign according to our data. Variant chr19-44327872-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3334894.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013380.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF112	NM_013380.4	MANE Select	c.2285G>A	p.Arg762Gln	missense	Exon 4 of 4	NP_037512.3
ZNF112	NM_001348281.2		c.2354G>A	p.Arg785Gln	missense	Exon 5 of 5	NP_001335210.1
ZNF112	NM_001083335.2		c.2303G>A	p.Arg768Gln	missense	Exon 5 of 5	NP_001076804.1	Q9UJU3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF112	ENST00000354340.9	TSL:1 MANE Select	c.2285G>A	p.Arg762Gln	missense	Exon 4 of 4	ENSP00000346305.3	Q9UJU3-2
ZNF112	ENST00000337401.8	TSL:1	c.2303G>A	p.Arg768Gln	missense	Exon 5 of 5	ENSP00000337081.3	Q9UJU3-1
ZNF112	ENST00000911245.1		c.2285G>A	p.Arg762Gln	missense	Exon 5 of 5	ENSP00000581304.1

Frequencies

GnomAD3 genomes

AF:

0.0000396

AC:

AN:

151474

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.0000737

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251158

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1461720

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727174

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.0000224

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000171

AC:

AN:

1111892

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

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:

0.0000396

AC:

AN:

151588

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74118

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41308

American (AMR)

AF:

0.00

AC:

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5100

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10540

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000737

AC:

AN:

67866

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

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:

0.0000596

Hom.:

Bravo

AF:

0.0000302

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.076

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.19

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.00050

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.33

M_CAP

Benign

0.0017

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.76

PhyloP100

-2.3

PrimateAI

Benign

0.36

PROVEAN

Benign

1.2

REVEL

Benign

0.016

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0060

Vest4

0.044

MVP

0.10

MPC

0.13

ClinPred

0.025

GERP RS

-5.0

Varity_R

0.024

gMVP

0.12

Mutation Taster

=91/9

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