rs6903823

chr6-28354519-A-G

Variant summary

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

The NM_024493.4(ZKSCAN3):c.-63+4452A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,140 control chromosomes in the GnomAD database, including 5,855 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 0.26 (5855 hom., cov: 33)
• Consequence: ZKSCAN3 NM_024493.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658

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]

ZSCAN31 (HGNC:14097): (zinc finger and SCAN domain containing 31) This gene encodes a protein containing multiple C2H2-type zinc finger motifs. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZKSCAN3	NM_024493.4	c.-63+4452A>G		intron_variant		ENST00000252211.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZKSCAN3	ENST00000252211.7	c.-63+4452A>G		intron_variant		1	NM_024493.4	P1
ZKSCAN3	ENST00000377255.3	c.-63+4131A>G		intron_variant		1		P1
ZKSCAN3	ENST00000341464.9	c.-43+4452A>G		intron_variant		2
ZSCAN31	ENST00000414429.5	c.-326-567T>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39469 AN: 152022 Hom.: 5839 Cov.: 33

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.260 AC: 39517 AN: 152140 Hom.: 5855 Cov.: 33 AF XY: 0.252 AC XY: 18780 AN XY: 74382

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.269

Alfa AF: 0.227 Hom.: 2140

Bravo AF: 0.275

Asia WGS AF: 0.228 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.5
Dann	Benign	0.37

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: rs6903823; hg19: chr6-28322296;