chr6-28153120-G-A

Variant names:

• chr6-28153120-G-A
• rs17774663
• NM_006298.4:c.840G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46
• Publications: 25 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006298.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZKSCAN8	NM_006298.4	MANE Select	c.840G>A	p.Gln280Gln	synonymous	Exon 6 of 6	NP_006289.2	Q15776-1
	ZKSCAN8	NM_001278119.2		c.840G>A	p.Gln280Gln	synonymous	Exon 7 of 7	NP_001265048.1	Q15776-1
	ZKSCAN8	NM_001278121.2		c.279G>A	p.Gln93Gln	synonymous	Exon 7 of 7	NP_001265050.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZKSCAN8	ENST00000330236.7	TSL:1 MANE Select	c.840G>A	p.Gln280Gln	synonymous	Exon 6 of 6	ENSP00000332750.5	Q15776-1
	ZKSCAN8	ENST00000457389.6	TSL:1	c.840G>A	p.Gln280Gln	synonymous	Exon 7 of 7	ENSP00000402948.2	Q15776-1
	ZKSCAN8	ENST00000606198.5	TSL:1	n.*377G>A		non_coding_transcript_exon	Exon 6 of 6	ENSP00000475589.1	Q15776-2

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

GnomAD2 exomes AF: 0.204 AC: 51189 AN: 251422 AF XY: 0.198

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

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

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

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: 40 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14566 AN: 67990

Other (OTH) AF: 0.219 AC: 464 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.056
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)

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

Other links and lift over

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