chr6-28364364-G-A

Position:

• chr6-28364364-G-A

Variant summary

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

The NM_024493.4(ZKSCAN3):​c.757+549G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0505 in 152,240 control chromosomes in the GnomAD database, including 316 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 0.051 (316 hom., cov: 32)
• Consequence: ZKSCAN3 NM_024493.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

Genes affected

ZKSCAN3 (HGNC:13853): (zinc finger with KRAB and SCAN domains 3) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and chromatin binding activity. Involved in several processes, including negative regulation of autophagy; negative regulation of cellular senescence; and regulation of transcription, DNA-templated. Located in cytoplasm and 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 (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZKSCAN3	NM_024493.4	c.757+549G>A		intron_variant		ENST00000252211.7	NP_077819.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZKSCAN3	ENST00000252211.7	c.757+549G>A		intron_variant		1	NM_024493.4	ENSP00000252211.2
ZKSCAN3	ENST00000377255.3	c.757+549G>A		intron_variant		1		ENSP00000366465.1
ZKSCAN3	ENST00000341464.9	c.313+549G>A		intron_variant		2		ENSP00000341883.5

Frequencies

GnomAD3 genomes AF: 0.0506 AC: 7696 AN: 152122 Hom.: 316 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0213

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0393

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0877

Gnomad OTH AF: 0.0335

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0505 AC: 7691 AN: 152240 Hom.: 316 Cov.: 32 AF XY: 0.0453 AC XY: 3372 AN XY: 74432

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.0212

Gnomad4 ASJ AF: 0.0207

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.0393

Gnomad4 NFE AF: 0.0877

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.0696 Hom.: 233

Bravo AF: 0.0482

Asia WGS AF: 0.00375 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.56
DANN	Benign	0.72

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: rs13214023; hg19: chr6-28332141;