20-290584-T-TTTA

Variant names:

• chr20-290584-T-TTTA
• rs3835237
• NM_153269.3:c.20+6_20+7insTAA

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380
• Publications: 5 publications found

Genes affected

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

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C20orf96	NM_153269.3	c.20+6_20+7insTAA		splice_region_variant, intron_variant	Intron 1 of 10	ENST00000360321.7	NP_695001.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C20orf96	ENST00000360321.7	c.20+6_20+7insTAA		splice_region_variant, intron_variant	Intron 1 of 10	1	NM_153269.3	ENSP00000353470.2
C20orf96	ENST00000400269.4	c.17+2_17+3insTAA		splice_donor_variant, intron_variant	Intron 1 of 10	1		ENSP00000383128.4
C20orf96	ENST00000382369.9	c.-245_-244insTAA		upstream_gene_variant		5		ENSP00000371806.5

Frequencies

GnomAD3 genomes AF: 0.249 AC: 33551 AN: 134948 Hom.: 5240 Cov.: 0

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

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.: 36 AF XY: 0.131 AC XY: 76539 AN XY: 582612

⚠️ 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.

GnomAD4 genome AF: 0.248 AC: 33543 AN: 134982 Hom.: 5241 Cov.: 0 AF XY: 0.245 AC XY: 15833 AN XY: 64746

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: 41 AN: 258

European-Non Finnish (NFE) AF: 0.322 AC: 20999 AN: 65146

Other (OTH) AF: 0.220 AC: 412 AN: 1874

Alfa AF: 0.0657 Hom.: 40

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3835237; hg19: chr20-271225;