12-133202374-C-A

Position:

• chr12-133202374-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003415.3(ZNF268):​c.688C>A​(p.His230Asn) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF268 NM_003415.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.27

Genes affected

ZNF268 (HGNC:13061): (zinc finger protein 268) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in several processes, including positive regulation of NIK/NF-kappaB signaling; positive regulation of nitrogen compound metabolic process; and regulation of apoptotic process. Located in actin cytoskeleton; cytosol; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000256825 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10210642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF268	NM_003415.3	c.688C>A	p.His230Asn	missense_variant	6/6	ENST00000536435.7	NP_003406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF268	ENST00000536435.7	c.688C>A	p.His230Asn	missense_variant	6/6	1	NM_003415.3	ENSP00000444412.3
ENSG00000256825	ENST00000540096.2	c.*212C>A		downstream_gene_variant		2		ENSP00000457704.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

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

Mar 06, 2023

The c.688C>A (p.H230N) alteration is located in exon 6 (coding exon 5) of the ZNF268 gene. This alteration results from a C to A substitution at nucleotide position 688, causing the histidine (H) at amino acid position 230 to be replaced by an asparagine (N). 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	0.065
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.24
DANN	Benign	0.39
DEOGEN2	Benign	0.0012	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.080	.;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.86	.;N
REVEL	Benign	0.017
Sift	Benign	0.31	.;T
Sift4G	Benign	0.32	T;T
Polyphen		0.0050	B;B
Vest4		0.17
MutPred		0.61		Loss of methylation at K232 (P = 0.0707);Loss of methylation at K232 (P = 0.0707);
MVP		0.085
MPC		0.026
ClinPred		0.021	T
GERP RS		-2.6
Varity_R		0.026
gMVP		0.021

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr12-133778960;