Genetic Variant ZNF599:p.Gly398Ser (chr19-34759609-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001007248.3(ZNF599):c.1192G>A(p.Gly398Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000286 in 1,608,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

ZNF599
NM_001007248.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.49

Publications

2 publications found

Variant links:

Genes affected

ZNF599 (HGNC:26408): (zinc finger protein 599) 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]

ZNF599 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01692155).

BP6

Variant 19-34759609-C-T is Benign according to our data. Variant chr19-34759609-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2463315.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007248.3. 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
	ZNF599	NM_001007248.3	MANE Select	c.1192G>A	p.Gly398Ser	missense	Exon 4 of 4	NP_001007249.1	Q96NL3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF599	ENST00000329285.13	TSL:2 MANE Select	c.1192G>A	p.Gly398Ser	missense	Exon 4 of 4	ENSP00000333802.6	Q96NL3-1
ZNF599	ENST00000673678.1		n.*1192G>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000501024.1	A0A669KB57
ZNF599	ENST00000673678.1		n.*1192G>A		3_prime_UTR	Exon 5 of 5	ENSP00000501024.1	A0A669KB57

Frequencies

GnomAD3 genomes

AF:

0.0000137

AC:

AN:

146424

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000253

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000215

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

GnomAD2 exomes

AF:

0.0000637

AC:

AN:

251274

AF XY:

0.0000515

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000435

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1461596

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727080

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.0000896

AC:

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.000328

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000697

AC:

AN:

86128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000989

AC:

AN:

1111944

Other (OTH)

AF:

0.000132

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

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:

0.0000137

AC:

AN:

146424

Hom.:

Cov.:

AF XY:

0.0000280

AC XY:

AN XY:

71546

show subpopulations

African (AFR)

AF:

0.0000253

AC:

AN:

39492

American (AMR)

AF:

0.00

AC:

AN:

14778

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3406

East Asian (EAS)

AF:

0.000215

AC:

AN:

4660

South Asian (SAS)

AF:

0.00

AC:

AN:

4544

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66108

Other (OTH)

AF:

0.00

AC:

AN:

2000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00

Hom.:

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

0.088

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.12

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.00056

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.000020

LIST_S2

Benign

0.023

M_CAP

Benign

0.0016

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.43

PhyloP100

-3.5

PrimateAI

Benign

0.25

PROVEAN

Benign

1.5

REVEL

Benign

0.012

Sift

Benign

0.48

Sift4G

Benign

0.94

Polyphen

0.0010

Vest4

0.17

MutPred

0.19

Gain of ubiquitination at K402 (P = 0.0846)

MVP

0.12

MPC

0.033

ClinPred

0.012

GERP RS

-0.89

Varity_R

0.038

gMVP

0.015

Mutation Taster

=98/2

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