NM_153269.3:c.20+6_20+7insTTA

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_153269.3(C20orf96):​c.20+6_20+7insTTA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,419,062 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: C20orf96 NM_153269.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380
• Publications: 0 publications found

Genes affected

C20orf96 (HGNC:16227): (chromosome 20 open reading frame 96)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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+7insTTA		splice_region intron	N/A	NP_695001.2
	C20orf96	NM_080571.2		c.17+2_17+3insTTA		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+7insTTA		splice_region intron	N/A	ENSP00000353470.2
	C20orf96	ENST00000400269.4	TSL:1	c.17+2_17+3insTTA		splice_donor intron	N/A	ENSP00000383128.4
	C20orf96	ENST00000382369.9	TSL:5	c.-245_-244insTTA		upstream_gene	N/A	ENSP00000371806.5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1419062 Hom.: 0 Cov.: 36 AF XY: 0.00000142 AC XY: 1 AN XY: 705200

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

African (AFR) AF: 0.00 AC: 0 AN: 30938

American (AMR) AF: 0.00 AC: 0 AN: 38758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25202

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 81278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48508

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

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1091812

Other (OTH) AF: 0.00 AC: 0 AN: 58656

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000812204), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

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;