Variant chr19-34759648-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001007248.3(ZNF599):c.1153C>G(p.His385Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000317 in 1,614,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

ZNF599
NM_001007248.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.63

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 made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.925

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF599	NM_001007248.3 link	c.1153C>G	p.His385Asp	missense_variant	4/4	ENST00000329285.13	NP_001007249.1	Q96NL3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF599	ENST00000329285.13 link	c.1153C>G	p.His385Asp	missense_variant	4/4	2	NM_001007248.3	ENSP00000333802.6	Q96NL3-1
ZNF599	ENST00000673678.1 link	n.*1153C>G		non_coding_transcript_exon_variant	5/5			ENSP00000501024.1	A0A669KB57
ZNF599	ENST00000673678.1 link	n.*1153C>G		3_prime_UTR_variant	5/5			ENSP00000501024.1	A0A669KB57

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000251

AC:

AN:

251446

Hom.:

AF XY:

0.000213

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000484

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000326

AC:

476

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000314

AC XY:

228

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000404

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000230

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.000345

Hom.:

Bravo

AF:

0.000189

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2024

The c.1153C>G (p.H385D) alteration is located in exon 4 (coding exon 4) of the ZNF599 gene. This alteration results from a C to G substitution at nucleotide position 1153, causing the histidine (H) at amino acid position 385 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.090

BayesDel_noAF

Pathogenic

0.24

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

Eigen

Pathogenic

0.82

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.47

M_CAP

Benign

0.084

MetaRNN

Pathogenic

0.92

MetaSVM

Uncertain

0.77

MutationAssessor

Pathogenic

4.4

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-8.9

REVEL

Pathogenic

0.74

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.78

MVP

0.97

MPC

0.28

ClinPred

0.98

GERP RS

2.5

Varity_R

0.77

gMVP

0.44

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over