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

Variant summary

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

The NM_153269.3(C20orf96):c.20+6_20+7insTAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,308,060 control chromosomes in the GnomAD database, including 6,561 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5241 hom., cov: 0)

Exomes 𝑓: 0.13 ( 1320 hom. )

Consequence

C20orf96
NM_153269.3 splice_region, 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 (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153269.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C20orf96	NM_153269.3	MANE Select	c.20+6_20+7insTAA		splice_region intron	N/A	NP_695001.2
	C20orf96	NM_080571.2		c.17+2_17+3insTAA		splice_donor intron	N/A	NP_542138.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
C20orf96	ENST00000360321.7	TSL:1 MANE Select	c.20+6_20+7insTAA	splice_region intron	N/A	ENSP00000353470.2
C20orf96	ENST00000400269.4	TSL:1	c.17+2_17+3insTAA	splice_donor intron	N/A	ENSP00000383128.4
C20orf96	ENST00000382369.9	TSL:5	c.-245_-244insTAA	upstream_gene	N/A	ENSP00000371806.5

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

33551

AN:

134948

Hom.:

5240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0825

Gnomad AMI

AF:

0.222

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.390

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.163

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.220

GnomAD2 exomes

AF:

0.0699

AC:

11884

AN:

170000

AF XY:

0.0687

show subpopulations

Gnomad AFR exome

AF:

0.0475

Gnomad AMR exome

AF:

0.0712

Gnomad ASJ exome

AF:

0.0689

Gnomad EAS exome

AF:

0.0891

Gnomad FIN exome

AF:

0.0933

Gnomad NFE exome

AF:

0.0686

Gnomad OTH exome

AF:

0.0698

GnomAD4 exome

AF:

0.134

AC:

157759

AN:

1173078

Hom.:

1320

Cov.:

AF XY:

0.131

AC XY:

76539

AN XY:

582612

show subpopulations

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

African (AFR)

AF:

0.0639

AC:

1790

AN:

28024

American (AMR)

AF:

0.0736

AC:

2494

AN:

33888

Ashkenazi Jewish (ASJ)

AF:

0.0929

AC:

2004

AN:

21568

East Asian (EAS)

AF:

0.160

AC:

5014

AN:

31372

South Asian (SAS)

AF:

0.0866

AC:

5931

AN:

68494

European-Finnish (FIN)

AF:

0.124

AC:

5197

AN:

41902

Middle Eastern (MID)

AF:

0.0655

AC:

302

AN:

4610

European-Non Finnish (NFE)

AF:

0.144

AC:

129129

AN:

894342

Other (OTH)

AF:

0.121

AC:

5898

AN:

48878

⚠️ 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: 0.338

Heterozygous variant carriers

8249

16498

24746

32995

41244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5360

10720

16080

21440

26800

<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:

0.248

AC:

33543

AN:

134982

Hom.:

5241

Cov.:

AF XY:

0.245

AC XY:

15833

AN XY:

64746

show subpopulations

African (AFR)

AF:

0.0825

AC:

2768

AN:

33534

American (AMR)

AF:

0.235

AC:

3255

AN:

13836

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

879

AN:

3368

East Asian (EAS)

AF:

0.390

AC:

1842

AN:

4722

South Asian (SAS)

AF:

0.263

AC:

1144

AN:

4342

European-Finnish (FIN)

AF:

0.286

AC:

2007

AN:

7018

Middle Eastern (MID)

AF:

0.159

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.322

AC:

20999

AN:

65146

Other (OTH)

AF:

0.220

AC:

412

AN:

1874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1023

2045

3068

4090

5113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<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:

0.0657

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