rs76542212

Variant names:

• chr6-28230344-C-T
• rs76542212
• ENST00000425468.6:c.577C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001199479.2(ZSCAN9):​c.577C>T​(p.Arg193*) 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 NM_001199479.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.568
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199479.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN9	NM_006299.5	MANE Select	c.569-2218C>T		intron	N/A	NP_006290.1	O15535-1
	ZSCAN9	NM_001199479.2		c.577C>T	p.Arg193*	stop_gained	Exon 4 of 5	NP_001186408.1	O15535-2
	ZSCAN9	NM_001199480.2		c.569-2218C>T		intron	N/A	NP_001186409.1	O15535-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN9	ENST00000425468.6	TSL:1	c.577C>T	p.Arg193*	stop_gained	Exon 4 of 5	ENSP00000404074.2	O15535-2
	ZSCAN9	ENST00000252207.10	TSL:1 MANE Select	c.569-2218C>T		intron	N/A	ENSP00000252207.5	O15535-1
	ZSCAN9	ENST00000526391.5	TSL:1	c.569-2218C>T		intron	N/A	ENSP00000476254.1	U3KQV4

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

GnomAD2 exomes AF: 0.0415 AC: 5340 AN: 128654 AF XY: 0.0425

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 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

African (AFR) AF: 0.00885 AC: 277 AN: 31296

American (AMR) AF: 0.0224 AC: 775 AN: 34550

Ashkenazi Jewish (ASJ) AF: 0.0333 AC: 827 AN: 24856

East Asian (EAS) AF: 0.00603 AC: 215 AN: 35628

South Asian (SAS) AF: 0.0225 AC: 1754 AN: 77820

European-Finnish (FIN) AF: 0.0666 AC: 2250 AN: 33796

Middle Eastern (MID) AF: 0.0630 AC: 356 AN: 5652

European-Non Finnish (NFE) AF: 0.0706 AC: 75932 AN: 1075706

Other (OTH) AF: 0.0573 AC: 3303 AN: 57604

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

African (AFR) AF: 0.0119 AC: 496 AN: 41508

American (AMR) AF: 0.0277 AC: 423 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0325 AC: 113 AN: 3472

East Asian (EAS) AF: 0.00733 AC: 38 AN: 5184

South Asian (SAS) AF: 0.0184 AC: 89 AN: 4828

European-Finnish (FIN) AF: 0.0693 AC: 733 AN: 10570

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0673 AC: 4578 AN: 68004

Other (OTH) AF: 0.0360 AC: 76 AN: 2110

Alfa AF: 0.0579 Hom.: 642

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 v4.9

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
PhyloP100		-0.57
Vest4		0.018
GERP RS		-3.4
Mutation Taster		=170/30	polymorphism (auto)

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

Other links and lift over

dbSNP: rs76542212; hg19: chr6-28198122; COSMIC: COSV107253860;