dbSNP rs540763931: ZNF268:p.Gln105Arg (chr12-133191987-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001165885.2(ZNF268):c.314A>G(p.Gln105Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

ZNF268
NM_001165885.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.225

Publications

0 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01286149).

BP6

Variant 12-133191987-A-G is Benign according to our data. Variant chr12-133191987-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2569858.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001165885.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF268	NM_003415.3	MANE Select	c.441A>G	p.Pro147Pro	synonymous	Exon 5 of 6	NP_003406.1	Q14587-1
ZNF268	NM_001165885.2		c.314A>G	p.Gln105Arg	missense	Exon 4 of 5	NP_001159357.1	F5H7L3
ZNF268	NM_001165886.2		c.113A>G	p.Gln38Arg	missense	Exon 3 of 4	NP_001159358.1	F5H670

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF268	ENST00000541211.6	TSL:1	c.314A>G	p.Gln105Arg	missense	Exon 4 of 5	ENSP00000442446.2	F5H7L3
ZNF268	ENST00000542711.6	TSL:1	c.113A>G	p.Gln38Arg	missense	Exon 3 of 4	ENSP00000437858.1	F5H670
ZNF268	ENST00000536435.7	TSL:1 MANE Select	c.441A>G	p.Pro147Pro	synonymous	Exon 5 of 6	ENSP00000444412.3	Q14587-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000104

AC:

AN:

249170

AF XY:

0.000104

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00145

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1460820

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726542

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.00

AC:

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.000756

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

86218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111216

Other (OTH)

AF:

0.0000663

AC:

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000460

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41564

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.539

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000341

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000827

AC:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.6

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.015

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.36

M_CAP

Benign

0.0010

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.0

PhyloP100

-0.23

PROVEAN

Benign

-0.50

REVEL

Benign

0.0080

Sift

Pathogenic

0.0

Sift4G

Benign

0.30

Vest4

0.25

MVP

0.030

ClinPred

0.016

GERP RS

0.64

PromoterAI

0.058

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over