6-28251883-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019110.5(ZKSCAN4):​c.98C>A​(p.Ser33Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,397,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0863415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZKSCAN4	NM_019110.5	c.98C>A	p.Ser33Tyr	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>A	p.Ser33Tyr	missense_variant	Exon 1 of 5	1	NM_019110.5	ENSP00000366509.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000520 AC: 1 AN: 192492 AF XY: 0.00000959

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000108

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1397942 Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1 AN XY: 690476

African (AFR) AF: 0.00 AC: 0 AN: 30804

American (AMR) AF: 0.00 AC: 0 AN: 31266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21626

East Asian (EAS) AF: 0.00 AC: 0 AN: 39224

South Asian (SAS) AF: 0.00 AC: 0 AN: 75814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5446

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1085806

Other (OTH) AF: 0.00 AC: 0 AN: 57428

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2724

Bravo AF: 0.00000756

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.75
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.8
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.030
Sift	Benign	0.45	T
Sift4G	Benign	1.0	T
Vest4		0.19
ClinPred		0.45	T
GERP RS		-0.38
PromoterAI		-0.063	Neutral
Varity_R		0.049
gMVP		0.56
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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;