rs76542212

Positions:

• chr6-28230344-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000425468.6(ZSCAN9):​c.577C>T​(p.Arg193Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0604 in 1,529,078 control chromosomes in the GnomAD database, including 3,289 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. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.044 (211 hom., cov: 32)
  • Exomes 𝑓: 0.062 (3078 hom.)
• Consequence: ZSCAN9 ENST00000425468.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.568

Genes affected

ZSCAN9 (HGNC:12984): (zinc finger and SCAN domain containing 9) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN9	NM_006299.5	c.569-2218C>T		intron_variant		ENST00000252207.10	NP_006290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSCAN9	ENST00000252207.10	c.569-2218C>T		intron_variant		1	NM_006299.5	ENSP00000252207	P2

Frequencies

GnomAD3 genomes AF: 0.0439 AC: 6668 AN: 152054 Hom.: 211 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0276

Gnomad ASJ AF: 0.0325

Gnomad EAS AF: 0.00731

Gnomad SAS AF: 0.0184

Gnomad FIN AF: 0.0693

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.0364

GnomAD3 exomes AF: 0.0415 AC: 5340 AN: 128654 Hom.: 167 AF XY: 0.0425 AC XY: 2969 AN XY: 69856

Gnomad AFR exome AF: 0.0101

Gnomad AMR exome AF: 0.0217

Gnomad ASJ exome AF: 0.0291

Gnomad EAS exome AF: 0.0118

Gnomad SAS exome AF: 0.0217

Gnomad FIN exome AF: 0.0681

Gnomad NFE exome AF: 0.0672

Gnomad OTH exome AF: 0.0495

GnomAD4 exome AF: 0.0622 AC: 85689 AN: 1376908 Hom.: 3078 Cov.: 30 AF XY: 0.0613 AC XY: 41655 AN XY: 679096

Gnomad4 AFR exome AF: 0.00885

Gnomad4 AMR exome AF: 0.0224

Gnomad4 ASJ exome AF: 0.0333

Gnomad4 EAS exome AF: 0.00603

Gnomad4 SAS exome AF: 0.0225

Gnomad4 FIN exome AF: 0.0666

Gnomad4 NFE exome AF: 0.0706

Gnomad4 OTH exome AF: 0.0573

GnomAD4 genome AF: 0.0438 AC: 6666 AN: 152170 Hom.: 211 Cov.: 32 AF XY: 0.0428 AC XY: 3184 AN XY: 74402

Gnomad4 AFR AF: 0.0119

Gnomad4 AMR AF: 0.0277

Gnomad4 ASJ AF: 0.0325

Gnomad4 EAS AF: 0.00733

Gnomad4 SAS AF: 0.0184

Gnomad4 FIN AF: 0.0693

Gnomad4 NFE AF: 0.0673

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0620 Hom.: 476

Bravo AF: 0.0398

TwinsUK AF: 0.0704 AC: 261

ALSPAC AF: 0.0791 AC: 305

ExAC AF: 0.0270 AC: 419

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.64
DANN	Benign	0.77
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00016	N
MutationTaster	Benign	1.0	A;N;N
Vest4		0.018
GERP RS		-3.4

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: rs76542212; hg19: chr6-28198122;