Variant 8-245895-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001042416.3(ZNF596):c.1048C>A(p.Leu350Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000551 in 1,613,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00057 ( 0 hom. )

Consequence

ZNF596
NM_001042416.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0130

Variant links:

Genes affected

ZNF596 (HGNC:27268): (zinc finger protein 596) 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]

ZNF596 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12619573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF596	NM_001042416.3 linkuse as main transcript	c.1048C>A	p.Leu350Ile	missense_variant	6/6	ENST00000398612.3	NP_001035881.1	Q8TC21-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF596	ENST00000398612.3 linkuse as main transcript	c.1048C>A	p.Leu350Ile	missense_variant	6/6	5	NM_001042416.3	ENSP00000381613.1	Q8TC21-1
ZNF596	ENST00000308811.8 linkuse as main transcript	c.1048C>A	p.Leu350Ile	missense_variant	6/6	1		ENSP00000310033.4	Q8TC21-1
ZNF596	ENST00000320552.6 linkuse as main transcript	c.1048C>A	p.Leu350Ile	missense_variant	6/6	4		ENSP00000318719.3	Q8TC21-1
ZNF596	ENST00000640035.1 linkuse as main transcript	c.417+631C>A		intron_variant		5		ENSP00000491031.1	A0A1W2PNU1

Frequencies

GnomAD3 genomes

AF:

0.000336

AC:

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000632

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000287

AC:

AN:

251130

Hom.:

AF XY:

0.000309

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000520

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000573

AC:

838

AN:

1461794

Hom.:

Cov.:

AF XY:

0.000553

AC XY:

402

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000729

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000336

AC:

AN:

151996

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000571

Hom.:

Bravo

AF:

0.000461

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000264

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000474

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

Jul 20, 2021

The c.1048C>A (p.L350I) alteration is located in exon 6 (coding exon 5) of the ZNF596 gene. This alteration results from a C to A substitution at nucleotide position 1048, causing the leucine (L) at amino acid position 350 to be replaced by an isoleucine (I). 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

0.60

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;T;T

Eigen

Benign

-0.0013

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.00020

LIST_S2

Benign

0.67

.;.;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.7

M;M;M

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.7

.;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0060

.;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.96

D;D;D

Vest4

0.15

MVP

0.62

MPC

0.0037

ClinPred

0.093

GERP RS

1.6

Varity_R

0.19

gMVP

0.074

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