Variant 1-26170115-G-C 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_015871.5(ZNF593):c.132G>C(p.Gln44His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000885 in 1,570,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000092 ( 0 hom. )

Consequence

ZNF593
NM_015871.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.327

Variant links:

Genes affected

ZNF593 (HGNC:30943): (zinc finger protein 593) Enables zinc ion binding activity. Involved in negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding activity and positive regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF593 links:

ZNF593OS (HGNC:41278): (ZNF593 opposite strand)

ZNF593OS links:

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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=0.076711744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF593	NM_015871.5 linkuse as main transcript	c.132G>C	p.Gln44His	missense_variant	1/3	ENST00000374266.7	NP_056955.2
ZNF593OS	NM_001395468.1 linkuse as main transcript	c.*517C>G		3_prime_UTR_variant	4/4	ENST00000433939.7	NP_001382397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF593	ENST00000374266.7 linkuse as main transcript	c.132G>C	p.Gln44His	missense_variant	1/3	1	NM_015871.5	ENSP00000363384	P1
ZNF593OS	ENST00000433939.7 linkuse as main transcript	c.*517C>G		3_prime_UTR_variant	4/4	3	NM_001395468.1	ENSP00000489416	P1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152246

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000575

AC:

AN:

174032

Hom.:

AF XY:

0.0000634

AC XY:

AN XY:

94700

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000746

Gnomad NFE exome

AF:

0.000126

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000917

AC:

130

AN:

1418348

Hom.:

Cov.:

AF XY:

0.0000883

AC XY:

AN XY:

702272

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000258

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000651

Gnomad4 NFE exome

AF:

0.000107

Gnomad4 OTH exome

AF:

0.000153

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000807

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:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000677

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000422

AC:

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

May 30, 2023

The c.132G>C (p.Q44H) alteration is located in exon 1 (coding exon 1) of the ZNF593 gene. This alteration results from a G to C substitution at nucleotide position 132, causing the glutamine (Q) at amino acid position 44 to be replaced by a histidine (H). 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

Benign

0.089

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.020

T;T

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.33

T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.30

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.97

N;N

REVEL

Benign

0.022

Sift

Benign

0.12

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.070

B;.

Vest4

0.091

MutPred

0.15

Gain of glycosylation at S40 (P = 0.1441);Gain of glycosylation at S40 (P = 0.1441);

MVP

0.37

MPC

0.63

ClinPred

0.047

GERP RS

2.4

Varity_R

0.092

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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