Genetic Variant ZNF268:p.Arg4Met (chr12-133182008-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001165882.3(ZNF268):c.-246G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,414,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

ZNF268
NM_001165882.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.82

Variant links:

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]

ZNF268 links:

ENSG00000256825 (HGNC:):

ENSG00000256825 links:

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ACMG classification

Classification made for transcript

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=0.13426745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF268	NM_003415.3 link	c.11G>T	p.Arg4Met	missense_variant	Exon 2 of 6	ENST00000536435.7	NP_003406.1	Q14587-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF268	ENST00000536435.7 link	c.11G>T	p.Arg4Met	missense_variant	Exon 2 of 6	1	NM_003415.3	ENSP00000444412.3		Q14587-1
ENSG00000256825	ENST00000540096.2 link	c.506G>T	p.Arg169Met	missense_variant	Exon 6 of 11	2		ENSP00000457704.2		A0A088AWK7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.07e-7

AC:

AN:

1414018

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698674

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000270

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.0031

.;.;T;T;T;.;T;.;.;.;.;.

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.68

T;T;.;T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.13

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.69

.;.;N;N;.;N;.;.;.;.;.;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.2

N;.;D;N;D;.;D;D;N;.;N;.

REVEL

Benign

0.10

Sift

Uncertain

0.011

D;.;D;D;D;.;D;D;D;.;D;.

Sift4G

Uncertain

0.041

D;D;D;D;D;D;D;.;D;D;D;D

Polyphen

0.62

.;.;P;P;.;.;.;.;.;.;.;.

Vest4

0.54

MutPred

0.36

.;Loss of methylation at R4 (P = 0.0092);Loss of methylation at R4 (P = 0.0092);Loss of methylation at R4 (P = 0.0092);Loss of methylation at R4 (P = 0.0092);Loss of methylation at R4 (P = 0.0092);Loss of methylation at R4 (P = 0.0092);Loss of methylation at R4 (P = 0.0092);Loss of methylation at R4 (P = 0.0092);Loss of methylation at R4 (P = 0.0092);Loss of methylation at R4 (P = 0.0092);Loss of methylation at R4 (P = 0.0092);

MVP

0.12

MPC

0.36

ClinPred

0.34

GERP RS

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.092

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over