chr20-290584-T-TTTTTTA

Variant names:

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

Variant summary

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

The NM_153269.3(C20orf96):​c.20+6_20+7insTAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 1,546,144 control chromosomes in the GnomAD database, including 65 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.014 (32 hom., cov: 0)
  • Exomes 𝑓: 0.0022 (33 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.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0138 (1860/135250) while in subpopulation AFR AF = 0.0339 (1137/33506). AF 95% confidence interval is 0.0323. There are 32 homozygotes in GnomAd4. There are 860 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 32 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153269.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C20orf96	NM_153269.3	MANE Select	c.20+6_20+7insTAAAAA		splice_region intron	N/A	NP_695001.2
	C20orf96	NM_080571.2		c.17+2_17+3insTAAAAA		splice_donor intron	N/A	NP_542138.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C20orf96	ENST00000360321.7	TSL:1 MANE Select	c.20+6_20+7insTAAAAA		splice_region intron	N/A	ENSP00000353470.2
	C20orf96	ENST00000400269.4	TSL:1	c.17+2_17+3insTAAAAA		splice_donor intron	N/A	ENSP00000383128.4
	C20orf96	ENST00000382369.9	TSL:5	c.-245_-244insTAAAAA		upstream_gene	N/A	ENSP00000371806.5

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 1861 AN: 135216 Hom.: 32 Cov.: 0

Gnomad AFR AF: 0.0340

Gnomad AMI AF: 0.0271

Gnomad AMR AF: 0.00584

Gnomad ASJ AF: 0.00148

Gnomad EAS AF: 0.000841

Gnomad SAS AF: 0.000687

Gnomad FIN AF: 0.000564

Gnomad MID AF: 0.00352

Gnomad NFE AF: 0.00889

Gnomad OTH AF: 0.0113

GnomAD4 exome AF: 0.00216 AC: 3051 AN: 1410894 Hom.: 33 Cov.: 36 AF XY: 0.00212 AC XY: 1486 AN XY: 701206

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

African (AFR) AF: 0.0114 AC: 343 AN: 30064

American (AMR) AF: 0.00119 AC: 46 AN: 38628

Ashkenazi Jewish (ASJ) AF: 0.000636 AC: 16 AN: 25152

East Asian (EAS) AF: 0.000310 AC: 12 AN: 38690

South Asian (SAS) AF: 0.00138 AC: 112 AN: 81100

European-Finnish (FIN) AF: 0.00116 AC: 56 AN: 48470

Middle Eastern (MID) AF: 0.000970 AC: 5 AN: 5154

European-Non Finnish (NFE) AF: 0.00215 AC: 2336 AN: 1085364

Other (OTH) AF: 0.00215 AC: 125 AN: 58272

⚠️ 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: 0.0138 AC: 1860 AN: 135250 Hom.: 32 Cov.: 0 AF XY: 0.0133 AC XY: 860 AN XY: 64896

African (AFR) AF: 0.0339 AC: 1137 AN: 33506

American (AMR) AF: 0.00583 AC: 81 AN: 13888

Ashkenazi Jewish (ASJ) AF: 0.00148 AC: 5 AN: 3378

East Asian (EAS) AF: 0.000844 AC: 4 AN: 4740

South Asian (SAS) AF: 0.000689 AC: 3 AN: 4354

European-Finnish (FIN) AF: 0.000564 AC: 4 AN: 7096

Middle Eastern (MID) AF: 0.00385 AC: 1 AN: 260

European-Non Finnish (NFE) AF: 0.00889 AC: 580 AN: 65268

Other (OTH) AF: 0.0112 AC: 21 AN: 1876

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
Mutation Taster		=100/0	polymorphism

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;