rs17774663

chr6-28153120-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006298.4(ZKSCAN8):c.840G>A(p.Gln280=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ZKSCAN8	NM_006298.4	c.840G>A	p.Gln280=	synonymous_variant	6/6	ENST00000330236.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZKSCAN8	ENST00000330236.7	c.840G>A	p.Gln280=	synonymous_variant	6/6	1	NM_006298.4	P1
ZKSCAN8	ENST00000457389.6	c.840G>A	p.Gln280=	synonymous_variant	7/7	1		P1
ZKSCAN8	ENST00000606198.5	c.*377G>A		3_prime_UTR_variant, NMD_transcript_variant	6/6	1
ZKSCAN8	ENST00000536028.2			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34865 AN: 151986 Hom.: 4145 Cov.: 32

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

GnomAD3 exomes AF: 0.204 AC: 51189 AN: 251422 Hom.: 5525 AF XY: 0.198 AC XY: 26932 AN XY: 135880

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 SAS exome AF: 0.139

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.: 33 AF XY: 0.219 AC XY: 159492 AN XY: 727234

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.237

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.218

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.185

Gnomad4 NFE exome AF: 0.232

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.229 AC: 34901 AN: 152104 Hom.: 4152 Cov.: 32 AF XY: 0.224 AC XY: 16624 AN XY: 74338

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.219

Alfa AF: 0.223 Hom.: 2596

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
Dann	Benign	0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs17774663; hg19: chr6-28120898; COSMIC: COSV57638339; COSMIC: COSV57638339;