16-71448661-T-C

Position:

• chr16-71448661-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001381984.1(ZNF23):​c.1493A>G​(p.Lys498Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF23 NM_001381984.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.44

Genes affected

ZNF23 (HGNC:13023): (zinc finger protein 23) Enables sequence-specific double-stranded 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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3770913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF23	NM_001381984.1	c.1493A>G	p.Lys498Arg	missense_variant	5/5	ENST00000647773.2	NP_001368913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF23	ENST00000647773.2	c.1493A>G	p.Lys498Arg	missense_variant	5/5		NM_001381984.1	ENSP00000497736	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000330 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 23, 2021

The c.1364A>G (p.K455R) alteration is located in exon 6 (coding exon 3) of the ZNF23 gene. This alteration results from a A to G substitution at nucleotide position 1364, causing the lysine (K) at amino acid position 455 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	Benign	0.18
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	.;.;T;T;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.31	T;T;.;.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.38	T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.3	.;.;L;L;L
MutationTaster	Benign	0.61	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.9	.;.;D;D;.
REVEL	Benign	0.20
Sift	Uncertain	0.025	.;.;D;D;.
Sift4G	Uncertain	0.0060	D;.;D;D;D
Polyphen		1.0	.;.;D;D;D
Vest4		0.41
MVP		0.47
MPC		0.41
ClinPred		0.96	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.016

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

LitVar

Other links and lift over

dbSNP: rs1272790097; hg19: chr16-71482564;