8-143650459-A-G

Variant names:

• chr8-143650459-A-G
• NM_001261843.2:c.467A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001261843.2(ZNF623):​c.467A>G​(p.Glu156Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF623 NM_001261843.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.677
• Publications: 0 publications found

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]

ACMG classification

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=0.134947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF623	NM_001261843.2	c.467A>G	p.Glu156Gly	missense_variant	Exon 2 of 2	ENST00000526926.6	NP_001248772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF623	ENST00000526926.6	c.467A>G	p.Glu156Gly	missense_variant	Exon 2 of 2	2	NM_001261843.2	ENSP00000435232.1
ZNF623	ENST00000458270.2	c.467A>G	p.Glu156Gly	missense_variant	Exon 2 of 2	1		ENSP00000411139.2
ZNF623	ENST00000501748.3	c.587A>G	p.Glu196Gly	missense_variant	Exon 1 of 1	6		ENSP00000445979.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.587A>G (p.E196G) alteration is located in exon 1 (coding exon 1) of the ZNF623 gene. This alteration results from a A to G substitution at nucleotide position 587, causing the glutamic acid (E) at amino acid position 196 to be replaced by a glycine (G). 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	0.74
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	.;.;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.0066	N
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.97	T
PhyloP100		-0.68
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.2	D;D;D
REVEL	Benign	0.032
Sift	Benign	0.21	T;T;T
Sift4G	Benign	0.36	T;T;T
Vest4		0.088
MutPred		0.22		.;.;Loss of catalytic residue at E196 (P = 0.0797);
MVP		0.32
MPC		0.40
ClinPred		0.77	D
GERP RS		3.2
gMVP		0.035
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

hg19: chr8-144732629;