Genetic Variant ZNF623:p.Cys38Tyr (chr8-143650105-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001261843.2(ZNF623):c.113G>A(p.Cys38Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ZNF623
NM_001261843.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.460

Publications

0 publications found

Variant links:

Genes affected

ZNF623 (HGNC:29084): (zinc finger protein 623) 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 by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF623 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0720883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF623	NM_001261843.2 link	c.113G>A	p.Cys38Tyr	missense_variant	Exon 2 of 2	ENST00000526926.6	NP_001248772.1	O75123-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF623	ENST00000526926.6 link	c.113G>A	p.Cys38Tyr	missense_variant	Exon 2 of 2	2	NM_001261843.2	ENSP00000435232.1	O75123-2
ZNF623	ENST00000458270.2 link	c.113G>A	p.Cys38Tyr	missense_variant	Exon 2 of 2	1		ENSP00000411139.2	O75123-2
ZNF623	ENST00000501748.3 link	c.233G>A	p.Cys78Tyr	missense_variant	Exon 1 of 1	6		ENSP00000445979.1	O75123-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112008

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.233G>A (p.C78Y) alteration is located in exon 1 (coding exon 1) of the ZNF623 gene. This alteration results from a G to A substitution at nucleotide position 233, causing the cysteine (C) at amino acid position 78 to be replaced by a tyrosine (Y). 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

0.077

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.3

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.014

.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0046

M_CAP

Benign

0.0039

MetaRNN

Benign

0.072

T;T;T

MetaSVM

Benign

-0.99

PhyloP100

-0.46

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.44

N;N;N

REVEL

Benign

0.028

Sift

Benign

0.57

T;T;T

Sift4G

Uncertain

0.021

D;D;D

Vest4

0.053

MutPred

0.43

.;.;Gain of phosphorylation at C78 (P = 0.0126);

MVP

0.24

MPC

0.47

ClinPred

0.013

GERP RS

0.92

PromoterAI

0.0084

Neutral

(source)

gMVP

0.049

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

8-143650105-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over