18-49483658-A-AG

Variant names:

• chr18-49483658-A-AG
• NM_001035005.4:c.90dupC

Variant summary

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

The NM_001035005.4(C18orf32):​c.90dupC​(p.Phe31LeufsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,446 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: C18orf32 NM_001035005.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: -0.568
• Publications: 1 publications found

Genes affected

C18orf32 (HGNC:31690): (chromosome 18 open reading frame 32) Involved in positive regulation of I-kappaB kinase/NF-kappaB signaling. Located in endoplasmic reticulum and lipid droplet. [provided by Alliance of Genome Resources, Apr 2022]

RPL17-C18orf32 (HGNC:44661): (RPL17-C18orf32 readthrough) This locus represents naturally occurring read-through transcription between the neighboring RPL17 (ribosomal protein L17) and C18orf32 (chromosome 18 open reading frame 32) genes. Alternative splicing results in multiple transcript variants. The encoded isoforms share sequence identity with the RPL17 protein, but they include frameshifted C-terminal regions derived from the downstream gene exons. [provided by RefSeq, Dec 2010]

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_001035005.4. 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
	C18orf32	NM_001035005.4	MANE Select	c.90dupC	p.Phe31LeufsTer3	frameshift	Exon 2 of 3	NP_001030177.1	Q8TCD1
	RPL17-C18orf32	NM_001199355.1		c.620dupC	p.Ser208PhefsTer47	frameshift	Exon 6 of 7	NP_001186284.1	A0A0A6YYL6
	RPL17-C18orf32	NM_001199356.2		c.506dupC	p.Ser170PhefsTer47	frameshift	Exon 6 of 7	NP_001186285.1	A0A0A0MRF8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C18orf32	ENST00000318240.8	TSL:1 MANE Select	c.90dupC	p.Phe31LeufsTer3	frameshift	Exon 2 of 3	ENSP00000323199.3	Q8TCD1
	RPL17-C18orf32	ENST00000584895.5	TSL:3	c.620dupC	p.Ser208PhefsTer47	frameshift	Exon 6 of 7	ENSP00000463379.1
	RPL17-C18orf32	ENST00000332968.11	TSL:5	c.506dupC	p.Ser170PhefsTer47	frameshift	Exon 6 of 7	ENSP00000352143.6	A0A0A0MRF8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461446 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727028

African (AFR) AF: 0.00 AC: 0 AN: 33440

American (AMR) AF: 0.00 AC: 0 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111940

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Glycosylphosphatidylinositol biosynthesis defect 25 (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr18-47010028;