rs192503972

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001099269.3(ZNF506):c.700T>C(p.Cys234Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000296 in 1,613,844 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 2 hom. )

Consequence

ZNF506
NM_001099269.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.49

Variant links:

Genes affected

ZNF506 (HGNC:23780): (zinc finger protein 506) 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, DNA-templated. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF506 links:

ZNF56P (HGNC:):

ZNF56P links:

ZNF56P (HGNC:13124): (zinc finger protein 56, pseudogene) 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]

ZNF56P 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=0.24266097).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF506	NM_001099269.3 link	c.700T>C	p.Cys234Arg	missense_variant	Exon 4 of 4	ENST00000540806.7	NP_001092739.1	Q5JVG8-1
ZNF506	NM_001145404.2 link	c.604T>C	p.Cys202Arg	missense_variant	Exon 3 of 3		NP_001138876.1	Q5JVG8-2
ZNF56P	NR_171023.1 link	n.421+18193A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF506	ENST00000540806.7 link	c.700T>C	p.Cys234Arg	missense_variant	Exon 4 of 4	2	NM_001099269.3	ENSP00000440625.1		Q5JVG8-1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000268

AC:

AN:

249774

AF XY:

0.000295

show subpopulations

Gnomad AFR exome

AF:

0.0000645

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000698

Gnomad NFE exome

AF:

0.000442

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000295

AC:

431

AN:

1461532

Hom.:

Cov.:

AF XY:

0.000267

AC XY:

194

AN XY:

727074

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00111

AC:

AN:

53204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000313

AC:

348

AN:

1111918

Other (OTH)

AF:

0.000381

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

116

145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000309

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41576

American (AMR)

AF:

0.0000654

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000573

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000646

Hom.:

Bravo

AF:

0.000140

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000363

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 24, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.700T>C (p.C234R) alteration is located in exon 4 (coding exon 4) of the ZNF506 gene. This alteration results from a T to C substitution at nucleotide position 700, causing the cysteine (C) at amino acid position 234 to be replaced by an arginine (R). 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

0.84

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;T;.

Eigen

Uncertain

0.39

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.035

T;.;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Uncertain

0.38

MutationAssessor

Pathogenic

3.5

H;H;.

PhyloP100

4.5

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-12

D;D;D

REVEL

Uncertain

0.35

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.15

MVP

0.91

MPC

0.86

ClinPred

0.97

GERP RS

0.97

Varity_R

0.88

gMVP

0.067

Mutation Taster

=96/4

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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rs192503972

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over