20-290584-T-TTTTA

Variant names:

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

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+7insTAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 1,472,022 control chromosomes in the GnomAD database, including 1,164 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.084 (749 hom., cov: 0)
  • Exomes 𝑓: 0.031 (415 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 (AFR) allele frequency at 95% confidence interval = 0.146 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+7insTAAA		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+7insTAAA		splice_region_variant, intron_variant	Intron 1 of 10	1	NM_153269.3	ENSP00000353470.2
C20orf96	ENST00000400269.4	c.17+2_17+3insTAAA		splice_donor_variant, intron_variant	Intron 1 of 10	1		ENSP00000383128.4
C20orf96	ENST00000382369.9	c.-245_-244insTAAA		upstream_gene_variant		5		ENSP00000371806.5

Frequencies

GnomAD3 genomes AF: 0.0840 AC: 11339 AN: 134992 Hom.: 747 Cov.: 0

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00903

Gnomad AMR AF: 0.0541

Gnomad ASJ AF: 0.0581

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.0882

Gnomad FIN AF: 0.0213

Gnomad MID AF: 0.0567

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.0699

GnomAD2 exomes AF: 0.0262 AC: 4451 AN: 170000 AF XY: 0.0256

Gnomad AFR exome AF: 0.0472

Gnomad AMR exome AF: 0.0194

Gnomad ASJ exome AF: 0.0239

Gnomad EAS exome AF: 0.0179

Gnomad FIN exome AF: 0.0280

Gnomad NFE exome AF: 0.0259

Gnomad OTH exome AF: 0.0274

GnomAD4 exome AF: 0.0312 AC: 41718 AN: 1336994 Hom.: 415 Cov.: 36 AF XY: 0.0304 AC XY: 20195 AN XY: 663756

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

African (AFR) AF: 0.0703 AC: 1920 AN: 27326

American (AMR) AF: 0.0153 AC: 570 AN: 37312

Ashkenazi Jewish (ASJ) AF: 0.0221 AC: 527 AN: 23884

East Asian (EAS) AF: 0.0144 AC: 540 AN: 37474

South Asian (SAS) AF: 0.0335 AC: 2518 AN: 75240

European-Finnish (FIN) AF: 0.0216 AC: 1020 AN: 47196

Middle Eastern (MID) AF: 0.0167 AC: 82 AN: 4896

European-Non Finnish (NFE) AF: 0.0319 AC: 32841 AN: 1028496

Other (OTH) AF: 0.0308 AC: 1700 AN: 55170

⚠️ 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: 0.0840 AC: 11347 AN: 135028 Hom.: 749 Cov.: 0 AF XY: 0.0806 AC XY: 5224 AN XY: 64810

African (AFR) AF: 0.149 AC: 4992 AN: 33396

American (AMR) AF: 0.0540 AC: 748 AN: 13860

Ashkenazi Jewish (ASJ) AF: 0.0581 AC: 196 AN: 3374

East Asian (EAS) AF: 0.0313 AC: 148 AN: 4736

South Asian (SAS) AF: 0.0880 AC: 382 AN: 4340

European-Finnish (FIN) AF: 0.0213 AC: 151 AN: 7088

Middle Eastern (MID) AF: 0.0615 AC: 16 AN: 260

European-Non Finnish (NFE) AF: 0.0702 AC: 4576 AN: 65214

Other (OTH) AF: 0.0694 AC: 130 AN: 1874

Alfa AF: 0.0242 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;