20-290584-T-TTTTTTTA

Variant names:

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

Variant summary

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

The NM_080571.2(C20orf96):​c.17+2_17+3insTAAAAAA variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000448 in 1,553,294 control chromosomes in the GnomAD database, including 13 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 0)
  • Exomes 𝑓: 0.00032 (11 hom.)
• Consequence: C20orf96 NM_080571.2 splice_donor, 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 GnomAd4 at 2 AR gene

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+7insTAAAAAA		splice_region intron	N/A	NP_695001.2	Q9NUD7
	C20orf96	NM_080571.2		c.17+2_17+3insTAAAAAA		splice_donor intron	N/A	NP_542138.1	F5GZA9

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.00182 AC: 246 AN: 135310 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00630

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000864

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000229

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000276

Gnomad OTH AF: 0.00215

GnomAD4 exome AF: 0.000317 AC: 449 AN: 1417952 Hom.: 11 Cov.: 36 AF XY: 0.000299 AC XY: 211 AN XY: 704668

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

African (AFR) AF: 0.00326 AC: 100 AN: 30700

American (AMR) AF: 0.000387 AC: 15 AN: 38736

Ashkenazi Jewish (ASJ) AF: 0.000238 AC: 6 AN: 25198

East Asian (EAS) AF: 0.00 AC: 0 AN: 38726

South Asian (SAS) AF: 0.000357 AC: 29 AN: 81246

European-Finnish (FIN) AF: 0.000206 AC: 10 AN: 48494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5172

European-Non Finnish (NFE) AF: 0.000239 AC: 261 AN: 1091074

Other (OTH) AF: 0.000478 AC: 28 AN: 58606

⚠️ 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: 0.00183 AC: 247 AN: 135342 Hom.: 2 Cov.: 0 AF XY: 0.00186 AC XY: 121 AN XY: 64950

African (AFR) AF: 0.00632 AC: 212 AN: 33554

American (AMR) AF: 0.000864 AC: 12 AN: 13896

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

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

South Asian (SAS) AF: 0.000230 AC: 1 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: 0.000276 AC: 18 AN: 65300

Other (OTH) AF: 0.00213 AC: 4 AN: 1878

Alfa AF: 0.00 Hom.: 40

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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;