rs3835237

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-290584-T-TTA
• chr20-290584-T-TTAA
• chr20-290584-T-TTTA
• chr20-290584-T-TTTAAA
• chr20-290584-T-TTTTA
• chr20-290584-T-TTTTTA
• chr20-290584-T-TTTTTAA
• chr20-290584-T-TTTTTTA
• chr20-290584-T-TTTTTTTA
• chr20-290584-T-TTTTTTTTA
• chr20-290584-T-TTTTTTTTTA
• chr20-290584-T-TTTTTTTTTTA
• chr20-290584-T-TTTTTTTTTTTA
• chr20-290584-T-TTTTTTTTTTTTA
• chr20-290584-T-TTTTTTTTTTTTTA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_080571.2(C20orf96):​c.17+2_17+3insTA variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0621 in 1,432,950 control chromosomes in the GnomAD database, including 1,200 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.017 (54 hom., cov: 0)
  • Exomes 𝑓: 0.067 (1146 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0165 (2236/135312) while in subpopulation AFR AF = 0.0304 (1021/33560). AF 95% confidence interval is 0.0289. There are 54 homozygotes in GnomAd4. There are 1066 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 54 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+7insTA		splice_region intron	N/A	NP_695001.2
	C20orf96	NM_080571.2		c.17+2_17+3insTA		splice_donor intron	N/A	NP_542138.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2231 AN: 135278 Hom.: 52 Cov.: 0

Gnomad AFR AF: 0.0305

Gnomad AMI AF: 0.0135

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.0178

Gnomad EAS AF: 0.00610

Gnomad SAS AF: 0.00641

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.0176

Gnomad NFE AF: 0.0121

Gnomad OTH AF: 0.0166

GnomAD2 exomes AF: 0.0668 AC: 11353 AN: 170000 AF XY: 0.0676

Gnomad AFR exome AF: 0.0438

Gnomad AMR exome AF: 0.0590

Gnomad ASJ exome AF: 0.0619

Gnomad EAS exome AF: 0.0736

Gnomad FIN exome AF: 0.0820

Gnomad NFE exome AF: 0.0726

Gnomad OTH exome AF: 0.0555

GnomAD4 exome AF: 0.0668 AC: 86708 AN: 1297638 Hom.: 1146 Cov.: 36 AF XY: 0.0663 AC XY: 42728 AN XY: 644620

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

African (AFR) AF: 0.0376 AC: 1108 AN: 29456

American (AMR) AF: 0.0505 AC: 1814 AN: 35950

Ashkenazi Jewish (ASJ) AF: 0.0514 AC: 1183 AN: 23002

East Asian (EAS) AF: 0.0865 AC: 2952 AN: 34122

South Asian (SAS) AF: 0.0490 AC: 3696 AN: 75418

European-Finnish (FIN) AF: 0.0746 AC: 3319 AN: 44500

Middle Eastern (MID) AF: 0.0358 AC: 174 AN: 4866

European-Non Finnish (NFE) AF: 0.0693 AC: 69114 AN: 996836

Other (OTH) AF: 0.0626 AC: 3348 AN: 53488

⚠️ 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: 0.0165 AC: 2236 AN: 135312 Hom.: 54 Cov.: 0 AF XY: 0.0164 AC XY: 1066 AN XY: 64926

African (AFR) AF: 0.0304 AC: 1021 AN: 33560

American (AMR) AF: 0.0115 AC: 160 AN: 13888

Ashkenazi Jewish (ASJ) AF: 0.0178 AC: 60 AN: 3376

East Asian (EAS) AF: 0.00612 AC: 29 AN: 4740

South Asian (SAS) AF: 0.00666 AC: 29 AN: 4354

European-Finnish (FIN) AF: 0.0137 AC: 97 AN: 7092

Middle Eastern (MID) AF: 0.0192 AC: 5 AN: 260

European-Non Finnish (NFE) AF: 0.0121 AC: 790 AN: 65278

Other (OTH) AF: 0.0176 AC: 33 AN: 1878

Alfa AF: 0.0414 Hom.: 40

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)

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;