20-290584-T-TTTTTTTTA

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_153269.3(C20orf96):​c.20+6_20+7insTAAAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000849 in 1,554,240 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00051 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000044 (2 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000510 AC: 69 AN: 135320 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000153

Gnomad OTH AF: 0.00107

GnomAD4 exome AF: 0.0000444 AC: 63 AN: 1418886 Hom.: 2 Cov.: 36 AF XY: 0.0000482 AC XY: 34 AN XY: 705106

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

African (AFR) AF: 0.000421 AC: 13 AN: 30896

American (AMR) AF: 0.000129 AC: 5 AN: 38754

Ashkenazi Jewish (ASJ) AF: 0.000119 AC: 3 AN: 25202

East Asian (EAS) AF: 0.00 AC: 0 AN: 38730

South Asian (SAS) AF: 0.0000369 AC: 3 AN: 81274

European-Finnish (FIN) AF: 0.0000825 AC: 4 AN: 48508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5180

European-Non Finnish (NFE) AF: 0.0000266 AC: 29 AN: 1091708

Other (OTH) AF: 0.000102 AC: 6 AN: 58634

⚠️ 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: 0.000510 AC: 69 AN: 135354 Hom.: 0 Cov.: 0 AF XY: 0.000400 AC XY: 26 AN XY: 64952

African (AFR) AF: 0.00188 AC: 63 AN: 33562

American (AMR) AF: 0.000216 AC: 3 AN: 13898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3378

East Asian (EAS) AF: 0.00 AC: 0 AN: 4740

South Asian (SAS) AF: 0.00 AC: 0 AN: 4354

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.0000153 AC: 1 AN: 65302

Other (OTH) AF: 0.00106 AC: 2 AN: 1878

Alfa AF: 0.00 Hom.: 40

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38

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;