rs9986596

Positions:

• chr6-28251883-G-A
• chr6-28251883-G-C
• chr6-28251883-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019110.5(ZKSCAN4):​c.98C>T​(p.Ser33Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,550,052 control chromosomes in the GnomAD database, including 17,974 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.15 (2008 hom., cov: 32)
  • Exomes 𝑓: 0.15 (15966 hom.)
• Consequence: ZKSCAN4 NM_019110.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.84

Genes affected

ZKSCAN4 (HGNC:13854): (zinc finger with KRAB and SCAN domains 4) Enables identical protein binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020773709).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZKSCAN4	NM_019110.5	c.98C>T	p.Ser33Phe	missense_variant	1/5	ENST00000377294.3	NP_061983.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZKSCAN4	ENST00000377294.3	c.98C>T	p.Ser33Phe	missense_variant	1/5	1	NM_019110.5	ENSP00000366509.2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23303 AN: 152050 Hom.: 2007 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0876

Gnomad FIN AF: 0.0671

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.140

GnomAD3 exomes AF: 0.131 AC: 25232 AN: 192492 Hom.: 1842 AF XY: 0.128 AC XY: 13368 AN XY: 104318

Gnomad AFR exome AF: 0.236

Gnomad AMR exome AF: 0.136

Gnomad ASJ exome AF: 0.0879

Gnomad EAS exome AF: 0.127

Gnomad SAS exome AF: 0.0978

Gnomad FIN exome AF: 0.0732

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.146 AC: 204534 AN: 1397884 Hom.: 15966 Cov.: 33 AF XY: 0.144 AC XY: 99359 AN XY: 690432

Gnomad4 AFR exome AF: 0.239

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.0792

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.0917

Gnomad4 FIN exome AF: 0.0735

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome AF: 0.153 AC: 23314 AN: 152168 Hom.: 2008 Cov.: 32 AF XY: 0.147 AC XY: 10926 AN XY: 74402

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0744

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.0881

Gnomad4 FIN AF: 0.0671

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.138

Alfa AF: 0.133 Hom.: 2059

Bravo AF: 0.164

TwinsUK AF: 0.172 AC: 638

ALSPAC AF: 0.162 AC: 626

ESP6500AA AF: 0.218 AC: 953

ESP6500EA AF: 0.138 AC: 1180

ExAC AF: 0.122 AC: 14805

Asia WGS AF: 0.102 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Benign	0.88
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.031
Sift	Benign	0.34	T
Sift4G	Benign	0.71	T
Polyphen		0.0060	B
Vest4		0.044
MPC		1.3
ClinPred		0.033	T
GERP RS		-0.38
Varity_R		0.067
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs9986596; hg19: chr6-28219661;