Genetic Variant ENST00000425468.6:c.577C>T (chr6-28230344-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The ENST00000425468.6(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
ENST00000425468.6 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.568

Publications

13 publications found

Variant links:

COSMIC-nc: COSV107253860

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]

ZSCAN9 links:

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new If you want to explore the variant's impact on the transcript ENST00000425468.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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: ENST00000425468.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0613

AC XY:

41655

AN XY:

679096

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

3589

7178

10766

14355

17944

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2852

5704

8556

11408

14260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0438

AC:

6666

AN:

152170

Hom.:

211

Cov.:

AF XY:

0.0428

AC XY:

3184

AN XY:

74402

show subpopulations

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:

AN:

5184

South Asian (SAS)

AF:

0.0184

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0693

AC:

733

AN:

10570

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0673

AC:

4578

AN:

68004

Other (OTH)

AF:

0.0360

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

312

623

935

1246

1558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0579

Hom.:

642

Bravo

AF:

0.0398

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.64

(source)

DANN

Benign

0.77

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00016

PhyloP100

-0.57

Mutation Taster

=170/30

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over