Genetic Variant C20orf96:c.20+6_20+7insTAAAA (chr20-290584-T-TTTTTA) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_080571.2(C20orf96):c.17+2_17+3insTAAAA variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,526,340 control chromosomes in the GnomAD database, including 306 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.034 ( 168 hom., cov: 0)

Exomes 𝑓: 0.0079 ( 138 hom. )

Consequence

C20orf96
NM_080571.2 splice_donor, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.380

Publications

5 publications found

Variant links:

Genes affected

C20orf96 (HGNC:16227): (chromosome 20 open reading frame 96)

C20orf96 links:

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ACMG classification

Classification was made for transcript

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

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080571.2. 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
	C20orf96	NM_153269.3	MANE Select	c.20+6_20+7insTAAAA		splice_region intron	N/A	NP_695001.2	Q9NUD7
	C20orf96	NM_080571.2		c.17+2_17+3insTAAAA		splice_donor intron	N/A	NP_542138.1	F5GZA9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C20orf96	ENST00000360321.7	TSL:1 MANE Select	c.20+6_20+7insTAAAA	splice_region intron	N/A	ENSP00000353470.2	Q9NUD7
C20orf96	ENST00000400269.4	TSL:1	c.17+2_17+3insTAAAA	splice_donor intron	N/A	ENSP00000383128.4	F5GZA9
C20orf96	ENST00000907056.1		c.20+6_20+7insTAAAA	splice_region intron	N/A	ENSP00000577115.1

Frequencies

GnomAD3 genomes

AF:

0.0338

AC:

4562

AN:

135124

Hom.:

168

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0794

Gnomad AMI

AF:

0.0530

Gnomad AMR

AF:

0.0228

Gnomad ASJ

AF:

0.0234

Gnomad EAS

AF:

0.00526

Gnomad SAS

AF:

0.0163

Gnomad FIN

AF:

0.00183

Gnomad MID

AF:

0.0423

Gnomad NFE

AF:

0.0198

Gnomad OTH

AF:

0.0318

GnomAD2 exomes

AF:

0.0102

AC:

1740

AN:

170000

AF XY:

0.0101

show subpopulations

Gnomad AFR exome

AF:

0.0282

Gnomad AMR exome

AF:

0.00632

Gnomad ASJ exome

AF:

0.00863

Gnomad EAS exome

AF:

0.00513

Gnomad FIN exome

AF:

0.00920

Gnomad NFE exome

AF:

0.0102

Gnomad OTH exome

AF:

0.00779

GnomAD4 exome

AF:

0.00795

AC:

11057

AN:

1391182

Hom.:

138

Cov.:

AF XY:

0.00789

AC XY:

5455

AN XY:

691452

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0357

AC:

1028

AN:

28768

American (AMR)

AF:

0.00519

AC:

199

AN:

38314

Ashkenazi Jewish (ASJ)

AF:

0.00666

AC:

165

AN:

24762

East Asian (EAS)

AF:

0.00148

AC:

AN:

38548

South Asian (SAS)

AF:

0.00786

AC:

628

AN:

79858

European-Finnish (FIN)

AF:

0.00482

AC:

233

AN:

48292

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

5016

European-Non Finnish (NFE)

AF:

0.00764

AC:

8182

AN:

1070246

Other (OTH)

AF:

0.00896

AC:

514

AN:

57378

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.304

Heterozygous variant carriers

860

1719

2579

3438

4298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

340

680

1020

1360

1700

<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:

0.0337

AC:

4558

AN:

135158

Hom.:

168

Cov.:

AF XY:

0.0328

AC XY:

2129

AN XY:

64868

show subpopulations

African (AFR)

AF:

0.0792

AC:

2649

AN:

33442

American (AMR)

AF:

0.0228

AC:

316

AN:

13882

Ashkenazi Jewish (ASJ)

AF:

0.0234

AC:

AN:

3376

East Asian (EAS)

AF:

0.00527

AC:

AN:

4740

South Asian (SAS)

AF:

0.0158

AC:

AN:

4354

European-Finnish (FIN)

AF:

0.00183

AC:

AN:

7096

Middle Eastern (MID)

AF:

0.0423

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.0198

AC:

1291

AN:

65250

Other (OTH)

AF:

0.0310

AC:

AN:

1872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

178

356

534

712

890

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.00799

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.38

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

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