chr16-71449594-C-A

Variant names:

• chr16-71449594-C-A
• rs72795864
• NM_001381984.1:c.560G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001381984.1(ZNF23):​c.560G>T​(p.Gly187Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000619 in 1,614,016 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00068 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00061 (1 hom.)
• Consequence: ZNF23 NM_001381984.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 14 publications found

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]

ZNF23 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000261611 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010702074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF23	NM_001381984.1	c.560G>T	p.Gly187Val	missense_variant	Exon 5 of 5	ENST00000647773.2	NP_001368913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF23	ENST00000647773.2	c.560G>T	p.Gly187Val	missense_variant	Exon 5 of 5		NM_001381984.1	ENSP00000497736.2
ENSG00000261611	ENST00000561908.1	n.*895G>T		non_coding_transcript_exon_variant	Exon 12 of 12	2		ENSP00000463741.1
ENSG00000261611	ENST00000561908.1	n.*895G>T		3_prime_UTR_variant	Exon 12 of 12	2		ENSP00000463741.1

Frequencies

GnomAD3 genomes AF: 0.000677 AC: 103 AN: 152122 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000422 AC: 106 AN: 251268 AF XY: 0.000427

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000695

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000613 AC: 896 AN: 1461776 Hom.: 1 Cov.: 32 AF XY: 0.000606 AC XY: 441 AN XY: 727182

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000380 AC: 17 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000510 AC: 44 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000711 AC: 791 AN: 1112004

Other (OTH) AF: 0.000729 AC: 44 AN: 60394

GnomAD4 genome AF: 0.000677 AC: 103 AN: 152240 Hom.: 1 Cov.: 33 AF XY: 0.000618 AC XY: 46 AN XY: 74432

African (AFR) AF: 0.000193 AC: 8 AN: 41540

American (AMR) AF: 0.00203 AC: 31 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000882 AC: 60 AN: 68004

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.0000331 Hom.: 728

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ExAC AF: 0.000445 AC: 54

EpiCase AF: 0.00136

EpiControl AF: 0.000889

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.55
DANN	Benign	0.97
DEOGEN2	Benign	0.028	.;.;T;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.000040	N
LIST_S2	Benign	0.40	T;T;.;.;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.011	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.42	.;.;N;N;N
PhyloP100		-1.6
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.10	.;.;N;N;D
REVEL	Benign	0.018
Sift	Uncertain	0.011	.;.;D;D;D
Sift4G	Uncertain	0.033	D;.;D;D;D
Polyphen		0.041	.;.;B;B;B
Vest4		0.33
MVP		0.29
MPC		0.10
ClinPred		0.014	T
GERP RS		-0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.033
gMVP		0.040
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: rs72795864; hg19: chr16-71483497;