Genetic Variant NM_006298.4:c.840G>A (chr6-28153120-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_006298.4(ZKSCAN8):c.840G>A(p.Gln280Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,613,966 control chromosomes in the GnomAD database, including 41,666 homozygotes. 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: 𝑓 0.23 ( 4152 hom., cov: 32)

Exomes 𝑓: 0.22 ( 37514 hom. )

Consequence

ZKSCAN8
NM_006298.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.46

Publications

25 publications found

Variant links:

Genes affected

ZKSCAN8 (HGNC:12983): (zinc finger with KRAB and SCAN domains 8) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZKSCAN8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP7

Synonymous conserved (PhyloP=-2.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZKSCAN8	NM_006298.4 link	c.840G>A	p.Gln280Gln	synonymous_variant	Exon 6 of 6	ENST00000330236.7	NP_006289.2	Q15776-1A0A024RCK7Q59HG5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZKSCAN8	ENST00000330236.7 link	c.840G>A	p.Gln280Gln	synonymous_variant	Exon 6 of 6	1	NM_006298.4	ENSP00000332750.5		Q15776-1

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34865

AN:

151986

Hom.:

4145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.284

Gnomad AMI

AF:

0.289

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.222

GnomAD2 exomes

AF:

0.204

AC:

51189

AN:

251422

AF XY:

0.198

show subpopulations

Gnomad AFR exome

AF:

0.281

Gnomad AMR exome

AF:

0.239

Gnomad ASJ exome

AF:

0.178

Gnomad EAS exome

AF:

0.164

Gnomad FIN exome

AF:

0.187

Gnomad NFE exome

AF:

0.212

Gnomad OTH exome

AF:

0.189

GnomAD4 exome

AF:

0.223

AC:

325845

AN:

1461862

Hom.:

37514

Cov.:

AF XY:

0.219

AC XY:

159492

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.284

AC:

9509

AN:

33478

American (AMR)

AF:

0.237

AC:

10593

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

4515

AN:

26134

East Asian (EAS)

AF:

0.218

AC:

8650

AN:

39700

South Asian (SAS)

AF:

0.139

AC:

11971

AN:

86258

European-Finnish (FIN)

AF:

0.185

AC:

9873

AN:

53420

Middle Eastern (MID)

AF:

0.119

AC:

684

AN:

5768

European-Non Finnish (NFE)

AF:

0.232

AC:

257667

AN:

1111990

Other (OTH)

AF:

0.205

AC:

12383

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

17542

35084

52627

70169

87711

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9076

18152

27228

36304

45380

<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:

0.229

AC:

34901

AN:

152104

Hom.:

4152

Cov.:

AF XY:

0.224

AC XY:

16624

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.284

AC:

11761

AN:

41474

American (AMR)

AF:

0.242

AC:

3691

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

585

AN:

3468

East Asian (EAS)

AF:

0.175

AC:

902

AN:

5164

South Asian (SAS)

AF:

0.143

AC:

690

AN:

4830

European-Finnish (FIN)

AF:

0.183

AC:

1938

AN:

10574

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.214

AC:

14566

AN:

67990

Other (OTH)

AF:

0.219

AC:

464

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1347

2694

4041

5388

6735

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<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:

0.223

Hom.:

2972

Bravo

AF:

0.240

Asia WGS

AF:

0.154

AC:

537

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.056

(source)

DANN

Benign

0.30

PhyloP100

-2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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