Genetic Variant NM_198535.3:c.1494C>T (chr19-9295910-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_198535.3(ZNF699):c.1494C>T(p.Ser498Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000288 in 1,613,182 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

ZNF699
NM_198535.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.44

Publications

1 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: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 19-9295910-G-A is Benign according to our data. Variant chr19-9295910-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3904993.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.44 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF699	NM_198535.3 link	c.1494C>T	p.Ser498Ser	synonymous_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.1494C>T	p.Ser498Ser	synonymous_variant	Exon 6 of 6	5	NM_198535.3	ENSP00000467723.1		Q32M78
ZNF699	ENST00000308650.4 link	c.1494C>T	p.Ser498Ser	synonymous_variant	Exon 5 of 5	1		ENSP00000311596.3		Q32M78

Frequencies

GnomAD3 genomes

AF:

0.000337

AC:

AN:

151188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000730

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00152

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00138

Gnomad SAS

AF:

0.00147

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000479

AC:

120

AN:

250694

AF XY:

0.000567

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00288

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000283

AC:

413

AN:

1461872

Hom.:

Cov.:

AF XY:

0.000315

AC XY:

229

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33480

American (AMR)

AF:

0.000335

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000153

AC:

AN:

26136

East Asian (EAS)

AF:

0.00242

AC:

AN:

39698

South Asian (SAS)

AF:

0.000904

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000165

AC:

183

AN:

1111996

Other (OTH)

AF:

0.000530

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

118

148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000344

AC:

AN:

151310

Hom.:

Cov.:

AF XY:

0.000338

AC XY:

AN XY:

73902

show subpopulations

African (AFR)

AF:

0.0000728

AC:

AN:

41232

American (AMR)

AF:

0.00152

AC:

AN:

15178

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3458

East Asian (EAS)

AF:

0.00158

AC:

AN:

5070

South Asian (SAS)

AF:

0.00147

AC:

AN:

4768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67816

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000183

Hom.:

Bravo

AF:

0.000408

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ZNF699: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.0

(source)

DANN

Benign

0.76

PhyloP100

-1.4

Mutation Taster

=100/0

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

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NM_198535.3:c.1494C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over