chr6-28251883-G-A

Variant names:

• chr6-28251883-G-A
• rs9986596
• NM_019110.5:c.98C>T

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 39 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZKSCAN4	NM_019110.5	c.98C>T	p.Ser33Phe	missense_variant	Exon 1 of 5	ENST00000377294.3	NP_061983.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZKSCAN4	ENST00000377294.3	c.98C>T	p.Ser33Phe	missense_variant	Exon 1 of 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

GnomAD2 exomes AF: 0.131 AC: 25232 AN: 192492 AF XY: 0.128

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 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

African (AFR) AF: 0.239 AC: 7371 AN: 30804

American (AMR) AF: 0.130 AC: 4077 AN: 31262

Ashkenazi Jewish (ASJ) AF: 0.0792 AC: 1712 AN: 21626

East Asian (EAS) AF: 0.151 AC: 5910 AN: 39222

South Asian (SAS) AF: 0.0917 AC: 6954 AN: 75804

European-Finnish (FIN) AF: 0.0735 AC: 3715 AN: 50526

Middle Eastern (MID) AF: 0.0709 AC: 386 AN: 5444

European-Non Finnish (NFE) AF: 0.153 AC: 166633 AN: 1085772

Other (OTH) AF: 0.135 AC: 7776 AN: 57424

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

African (AFR) AF: 0.226 AC: 9362 AN: 41484

American (AMR) AF: 0.137 AC: 2103 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0744 AC: 258 AN: 3470

East Asian (EAS) AF: 0.121 AC: 626 AN: 5158

South Asian (SAS) AF: 0.0881 AC: 424 AN: 4814

European-Finnish (FIN) AF: 0.0671 AC: 712 AN: 10608

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9391 AN: 68010

Other (OTH) AF: 0.138 AC: 292 AN: 2116

Alfa AF: 0.134 Hom.: 2724

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
PhyloP100		2.8
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
PromoterAI		-0.10	Neutral
Varity_R		0.067
gMVP		0.59
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9986596; hg19: chr6-28219661; COSMIC: COSV107493977;