Variant rs7975069 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003415.3(ZNF268):c.524C>T(p.Thr175Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,606,872 control chromosomes in the GnomAD database, including 92,427 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.34 ( 9410 hom., cov: 33)

Exomes 𝑓: 0.33 ( 83017 hom. )

Consequence

ZNF268
NM_003415.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.828

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.8822503E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF268	NM_003415.3 linkuse as main transcript	c.524C>T	p.Thr175Met	missense_variant	6/6	ENST00000536435.7	NP_003406.1	Q14587-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF268	ENST00000536435.7 linkuse as main transcript	c.524C>T	p.Thr175Met	missense_variant	6/6	1	NM_003415.3	ENSP00000444412.3		Q14587-1
ENSG00000256825	ENST00000540096.2 linkuse as main transcript	c.*48C>T		3_prime_UTR_variant	11/11	2		ENSP00000457704.2		A0A088AWK7

Frequencies

GnomAD3 genomes

AF:

0.344

AC:

52171

AN:

151694

Hom.:

9402

Cov.:

show subpopulations

Gnomad AFR

AF:

0.414

Gnomad AMI

AF:

0.286

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.326

Gnomad EAS

AF:

0.0868

Gnomad SAS

AF:

0.280

Gnomad FIN

AF:

0.327

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.300

GnomAD3 exomes

AF:

0.308

AC:

74980

AN:

243244

Hom.:

12304

AF XY:

0.309

AC XY:

40712

AN XY:

131862

show subpopulations

Gnomad AFR exome

AF:

0.415

Gnomad AMR exome

AF:

0.256

Gnomad ASJ exome

AF:

0.331

Gnomad EAS exome

AF:

0.0733

Gnomad SAS exome

AF:

0.290

Gnomad FIN exome

AF:

0.322

Gnomad NFE exome

AF:

0.347

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.333

AC:

484960

AN:

1455060

Hom.:

83017

Cov.:

AF XY:

0.333

AC XY:

240496

AN XY:

723214

show subpopulations

Gnomad4 AFR exome

AF:

0.422

Gnomad4 AMR exome

AF:

0.255

Gnomad4 ASJ exome

AF:

0.334

Gnomad4 EAS exome

AF:

0.0779

Gnomad4 SAS exome

AF:

0.292

Gnomad4 FIN exome

AF:

0.320

Gnomad4 NFE exome

AF:

0.347

Gnomad4 OTH exome

AF:

0.321

GnomAD4 genome

AF:

0.344

AC:

52210

AN:

151812

Hom.:

9410

Cov.:

AF XY:

0.338

AC XY:

25108

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.414

Gnomad4 AMR

AF:

0.278

Gnomad4 ASJ

AF:

0.326

Gnomad4 EAS

AF:

0.0872

Gnomad4 SAS

AF:

0.280

Gnomad4 FIN

AF:

0.327

Gnomad4 NFE

AF:

0.346

Gnomad4 OTH

AF:

0.300

Alfa

AF:

0.336

Hom.:

14537

Bravo

AF:

0.341

TwinsUK

AF:

0.355

AC:

1318

ALSPAC

AF:

0.346

AC:

1335

ESP6500AA

AF:

0.408

AC:

1522

ESP6500EA

AF:

0.331

AC:

2710

ExAC

AF:

0.314

AC:

37879

Asia WGS

AF:

0.206

AC:

718

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.14

DANN

Benign

0.31

DEOGEN2

Benign

0.011

T;.;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.53

T;T;T;T

MetaRNN

Benign

0.00069

T;T;T;T

MetaSVM

Benign

-0.94

PROVEAN

Uncertain

-3.8

.;.;D;D

REVEL

Benign

0.011

Sift

Benign

0.099

.;.;T;T

Sift4G

Uncertain

0.010

D;D;D;D

Vest4

0.12

ClinPred

0.00098

GERP RS

-0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over