16-71449594-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001381984.1(ZNF23):​c.560G>C​(p.Gly187Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,613,924 control chromosomes in the GnomAD database, including 15,671 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.12 (1267 hom., cov: 33)
  • Exomes 𝑓: 0.13 (14404 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014417171).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF23	NM_001381984.1	c.560G>C	p.Gly187Ala	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>C	p.Gly187Ala	missense_variant	Exon 5 of 5		NM_001381984.1	ENSP00000497736.2
ENSG00000261611	ENST00000561908.1	n.*895G>C		non_coding_transcript_exon_variant	Exon 12 of 12	2		ENSP00000463741.1
ENSG00000261611	ENST00000561908.1	n.*895G>C		3_prime_UTR_variant	Exon 12 of 12	2		ENSP00000463741.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18786 AN: 152090 Hom.: 1267 Cov.: 33

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.0727

Gnomad ASJ AF: 0.0479

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.0393

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.0908

GnomAD2 exomes AF: 0.103 AC: 25860 AN: 251268 AF XY: 0.102

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.0481

Gnomad ASJ exome AF: 0.0515

Gnomad EAS exome AF: 0.00326

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.105

GnomAD4 exome AF: 0.134 AC: 195223 AN: 1461716 Hom.: 14404 Cov.: 32 AF XY: 0.131 AC XY: 94918 AN XY: 727144

African (AFR) AF: 0.134 AC: 4497 AN: 33478

American (AMR) AF: 0.0520 AC: 2327 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0492 AC: 1286 AN: 26132

East Asian (EAS) AF: 0.00597 AC: 237 AN: 39698

South Asian (SAS) AF: 0.0495 AC: 4272 AN: 86258

European-Finnish (FIN) AF: 0.130 AC: 6925 AN: 53306

Middle Eastern (MID) AF: 0.0720 AC: 415 AN: 5766

European-Non Finnish (NFE) AF: 0.151 AC: 168363 AN: 1111960

Other (OTH) AF: 0.114 AC: 6901 AN: 60394

GnomAD4 genome AF: 0.123 AC: 18791 AN: 152208 Hom.: 1267 Cov.: 33 AF XY: 0.118 AC XY: 8772 AN XY: 74412

African (AFR) AF: 0.133 AC: 5519 AN: 41530

American (AMR) AF: 0.0726 AC: 1109 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0479 AC: 166 AN: 3468

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5182

South Asian (SAS) AF: 0.0395 AC: 191 AN: 4834

European-Finnish (FIN) AF: 0.122 AC: 1291 AN: 10598

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10081 AN: 67994

Other (OTH) AF: 0.0894 AC: 189 AN: 2114

Alfa AF: 0.115 Hom.: 728

Bravo AF: 0.121

TwinsUK AF: 0.166 AC: 615

ALSPAC AF: 0.156 AC: 601

ESP6500AA AF: 0.137 AC: 601

ESP6500EA AF: 0.139 AC: 1193

ExAC AF: 0.108 AC: 13125

Asia WGS AF: 0.0350 AC: 122 AN: 3478

EpiCase AF: 0.130

EpiControl AF: 0.127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.27
DANN	Benign	0.97
DEOGEN2	Benign	0.034	.;.;T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.000030	N
LIST_S2	Benign	0.59	T;T;.;.;T
MetaRNN	Benign	0.0014	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.37	.;.;N;N;N
PhyloP100		-1.6
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.49	.;.;N;N;D
REVEL	Benign	0.0030
Sift	Benign	0.037	.;.;D;D;D
Sift4G	Uncertain	0.013	D;.;D;D;D
Polyphen		0.0	.;.;B;B;B
Vest4		0.15
MPC		0.085
ClinPred		0.0025	T
GERP RS		-0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.030
gMVP		0.029
Mutation Taster		=99/1	polymorphism (auto)

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; COSMIC: COSV61840564; COSMIC: COSV61840564;