Genetic Variant ZNF699:p.Arg443Gly (chr19-9296077-G-C) – 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_198535.3(ZNF699):c.1327C>G(p.Arg443Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R443Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF699
NM_198535.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.761

Publications

0 publications found

Variant links:

Genes affected

ZNF699 (HGNC:24750): (zinc finger protein 699) 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]

ZNF699 Gene-Disease associations (from GenCC):

DEGCAGS syndrome
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ZNF699 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=0.013342142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF699	NM_198535.3 link	c.1327C>G	p.Arg443Gly	missense_variant	Exon 6 of 6	ENST00000591998.6	NP_940937.1	Q32M78

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF699	ENST00000591998.6 link	c.1327C>G	p.Arg443Gly	missense_variant	Exon 6 of 6	5	NM_198535.3	ENSP00000467723.1		Q32M78
ZNF699	ENST00000308650.4 link	c.1327C>G	p.Arg443Gly	missense_variant	Exon 5 of 5	1		ENSP00000311596.3		Q32M78

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

138084

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1443902

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718032

African (AFR)

AF:

0.00

AC:

AN:

32924

American (AMR)

AF:

0.00

AC:

AN:

41914

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25604

East Asian (EAS)

AF:

0.00

AC:

AN:

38300

South Asian (SAS)

AF:

0.00

AC:

AN:

83194

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103532

Other (OTH)

AF:

0.00

AC:

AN:

59544

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

138216

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

67654

African (AFR)

AF:

0.00

AC:

AN:

36978

American (AMR)

AF:

0.00

AC:

AN:

13974

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3278

East Asian (EAS)

AF:

0.00

AC:

AN:

4344

South Asian (SAS)

AF:

0.00

AC:

AN:

4218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9708

Middle Eastern (MID)

AF:

0.00

AC:

AN:

172

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62862

Other (OTH)

AF:

0.00

AC:

AN:

1900

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.022

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.55

.;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.95

N;N

PhyloP100

0.76

PrimateAI

Benign

0.38

PROVEAN

Benign

5.7

.;N

REVEL

Benign

0.023

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0020

B;B

Vest4

0.14

MutPred

0.44

Loss of solvent accessibility (P = 0.0044);Loss of solvent accessibility (P = 0.0044);

MVP

0.17

MPC

0.17

ClinPred

0.067

GERP RS

-1.9

Varity_R

0.094

gMVP

0.070

Mutation Taster

=90/10

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over