chr8-143650327-C-A

Variant names:

• chr8-143650327-C-A
• rs770007205
• NM_001261843.2:c.335C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001261843.2(ZNF623):​c.335C>A​(p.Thr112Lys) 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. 15/20 in silico tools predict 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. T112M) 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: -2.67
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.011105597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF623	NM_001261843.2	c.335C>A	p.Thr112Lys	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.335C>A	p.Thr112Lys	missense_variant	Exon 2 of 2	2	NM_001261843.2	ENSP00000435232.1
ZNF623	ENST00000458270.2	c.335C>A	p.Thr112Lys	missense_variant	Exon 2 of 2	1		ENSP00000411139.2
ZNF623	ENST00000501748.3	c.455C>A	p.Thr152Lys	missense_variant	Exon 1 of 1	6		ENSP00000445979.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251104 AF XY: 0.00000737

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.079
DANN	Benign	0.88
DEOGEN2	Benign	0.0020	.;.;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0014	N
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.011	T;T;T
MetaSVM	Benign	-0.97	T
PhyloP100		-2.7
PrimateAI	Benign	0.19	T
PROVEAN	Benign	1.7	N;N;N
REVEL	Benign	0.023
Sift	Benign	0.70	T;T;T
Sift4G	Benign	0.70	T;T;T
Vest4		0.099
MutPred		0.34		.;.;Gain of methylation at T152 (P = 6e-04);
MVP		0.12
MPC		0.34
ClinPred		0.035	T
GERP RS		-5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.027
Mutation Taster		=100/0	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: rs770007205; hg19: chr8-144732497;