chr8-143650645-C-A

Variant names:

• chr8-143650645-C-A
• rs774885956
• NM_001261843.2:c.653C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001261843.2(ZNF623):​c.653C>A​(p.Thr218Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T218M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF623 NM_001261843.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30591714).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF623	NM_001261843.2	c.653C>A	p.Thr218Lys	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.653C>A	p.Thr218Lys	missense_variant	Exon 2 of 2	2	NM_001261843.2	ENSP00000435232.1
ZNF623	ENST00000458270.2	c.653C>A	p.Thr218Lys	missense_variant	Exon 2 of 2	1		ENSP00000411139.2
ZNF623	ENST00000501748.3	c.773C>A	p.Thr258Lys	missense_variant	Exon 1 of 1	6		ENSP00000445979.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.098	.;.;T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.26	N
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.98	T
PhyloP100		4.0
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-5.6	D;D;D
REVEL	Benign	0.10
Sift	Uncertain	0.0090	D;D;D
Sift4G	Uncertain	0.0090	D;D;D
Vest4		0.29
MutPred		0.42		.;.;Gain of methylation at T258 (P = 0.0027);
MVP		0.46
MPC		1.1
ClinPred		0.96	D
GERP RS		3.4
gMVP		0.17
Mutation Taster		=90/10	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

dbSNP: rs774885956; hg19: chr8-144732815;