16-71448934-T-C

Position:

• chr16-71448934-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.1220A>G​(p.Tyr407Cys) 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: -2.07

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]

ENSG00000261611 (HGNC:):

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=0.32246608).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF23	NM_001381984.1	c.1220A>G	p.Tyr407Cys	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.1220A>G	p.Tyr407Cys	missense_variant	5/5		NM_001381984.1	ENSP00000497736.2
ENSG00000261611	ENST00000561908.1	n.*1555A>G		non_coding_transcript_exon_variant	12/12	2		ENSP00000463741.1
ENSG00000261611	ENST00000561908.1	n.*1555A>G		3_prime_UTR_variant	12/12	2		ENSP00000463741.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Aug 11, 2022

The c.1091A>G (p.Y364C) 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 1091, causing the tyrosine (Y) at amino acid position 364 to be replaced by a cysteine (C). 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	Uncertain	0.48
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	.;.;T;T;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.000030	N
LIST_S2	Benign	0.29	T;T;.;.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.32	T;T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.7	.;.;M;M;M
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-8.0	.;.;D;D;.
REVEL	Benign	0.12
Sift	Uncertain	0.0010	.;.;D;D;.
Sift4G	Pathogenic	0.0010	D;.;D;D;D
Polyphen		0.015	.;.;B;B;B
Vest4		0.22
MutPred		0.57		.;.;Gain of ubiquitination at K362 (P = 0.0495);Gain of ubiquitination at K362 (P = 0.0495);Gain of ubiquitination at K362 (P = 0.0495);
MVP		0.36
MPC		0.12
ClinPred		0.99	D
GERP RS		-5.8
Varity_R		0.48
gMVP		0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-71482837;