dbSNP rs7975069: ZNF268:p.Thr175Met (chr12-133202210-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T175T) has been classified as Likely benign.

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

Publications

36 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF268	NM_003415.3 link	c.524C>T	p.Thr175Met	missense_variant	Exon 6 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.524C>T	p.Thr175Met	missense_variant	Exon 6 of 6	1	NM_003415.3	ENSP00000444412.3		Q14587-1
ENSG00000256825	ENST00000540096.2 link	c.*48C>T		3_prime_UTR_variant	Exon 11 of 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

GnomAD2 exomes

AF:

0.308

AC:

74980

AN:

243244

AF XY:

0.309

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 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

African (AFR)

AF:

0.422

AC:

14032

AN:

33238

American (AMR)

AF:

0.255

AC:

11120

AN:

43620

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

8642

AN:

25866

East Asian (EAS)

AF:

0.0779

AC:

3087

AN:

39604

South Asian (SAS)

AF:

0.292

AC:

24850

AN:

84978

European-Finnish (FIN)

AF:

0.320

AC:

17004

AN:

53176

Middle Eastern (MID)

AF:

0.289

AC:

1661

AN:

5738

European-Non Finnish (NFE)

AF:

0.347

AC:

385240

AN:

1108708

Other (OTH)

AF:

0.321

AC:

19324

AN:

60132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

15896

31792

47689

63585

79481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12260

24520

36780

49040

61300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.344

AC:

52210

AN:

151812

Hom.:

9410

Cov.:

AF XY:

0.338

AC XY:

25108

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.414

AC:

17146

AN:

41412

American (AMR)

AF:

0.278

AC:

4238

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.326

AC:

1131

AN:

3468

East Asian (EAS)

AF:

0.0872

AC:

450

AN:

5160

South Asian (SAS)

AF:

0.280

AC:

1344

AN:

4808

European-Finnish (FIN)

AF:

0.327

AC:

3442

AN:

10514

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.346

AC:

23487

AN:

67906

Other (OTH)

AF:

0.300

AC:

633

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1752

3504

5257

7009

8761

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

506

1012

1518

2024

2530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.338

Hom.:

19154

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

(source)

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

PhyloP100

-0.83

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

Varity_R

0.0070

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over