17-64075251-TAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr17-64075251-T-TAAAAAAAAAAAAA
• rs5821420
• NM_001433.5:c.283-17_283-5dupTTTTTTTTTTTTT

Variant summary

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

The NM_001433.5(ERN1):​c.283-17_283-5dupTTTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ERN1 NM_001433.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278
• Publications: 1 publications found

Genes affected

ERN1 (HGNC:3449): (endoplasmic reticulum to nucleus signaling 1) This gene encodes the transmembrane protein kinase inositol-requiring enzyme 1. The encoded protein contains two functional catalytic domains, a serine/threonine-protein kinase domain and an endoribonuclease domain. This protein functions as a sensor of unfolded proteins in the endoplasmic reticulum (ER) and triggers an intracellular signaling pathway termed the unfolded protein response (UPR). The UPR is an ER stress response that is conserved from yeast to mammals and activates genes involved in degrading misfolded proteins, regulating protein synthesis and activating molecular chaperones. This protein specifically mediates the splicing and activation of the stress response transcription factor X-box binding protein 1. [provided by RefSeq, Aug 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001433.5. 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
	ERN1	NM_001433.5	MANE Select	c.283-17_283-5dupTTTTTTTTTTTTT		splice_region intron	N/A	NP_001424.3	O75460-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERN1	ENST00000433197.4	TSL:1 MANE Select	c.283-5_283-4insTTTTTTTTTTTTT		splice_region intron	N/A	ENSP00000401445.2	O75460-1
	ERN1	ENST00000680433.1		c.283-5_283-4insTTTTTTTTTTTTT		splice_region intron	N/A	ENSP00000506094.1	A0A7P0TAB0
	ERN1	ENST00000577567.5	TSL:5	n.148-5_148-4insTTTTTTTTTTTTT		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 136066 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1152810 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 571964

African (AFR) AF: 0.00 AC: 0 AN: 21962

American (AMR) AF: 0.00 AC: 0 AN: 14784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19768

East Asian (EAS) AF: 0.00 AC: 0 AN: 28338

South Asian (SAS) AF: 0.00 AC: 0 AN: 61076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4354

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 915586

Other (OTH) AF: 0.00 AC: 0 AN: 48288

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 136066 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 65194

African (AFR) AF: 0.00 AC: 0 AN: 34224

American (AMR) AF: 0.00 AC: 0 AN: 13912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3358

East Asian (EAS) AF: 0.00 AC: 0 AN: 4888

South Asian (SAS) AF: 0.00 AC: 0 AN: 4440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65354

Other (OTH) AF: 0.00 AC: 0 AN: 1888

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.28

Splicing

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

Other links and lift over

dbSNP: rs5821420; hg19: chr17-62152611;