16-56935458-CCA-GCT

Variant names:

• chr16-56935458-CCA-GCT
• NM_014685.4:c.283_285delCCAinsGCT
• HERPUD1 p.Pro95Ala

Variant summary

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

The NM_001436352.1(HERPUD1):​c.83_85delCCAinsGCT​(p.AlaArg28*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, 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: not found (cov: 32)
• Consequence: HERPUD1 NM_001436352.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 0 publications found

Genes affected

HERPUD1 (HGNC:13744): (homocysteine inducible ER protein with ubiquitin like domain 1) The accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers the ER stress response. This response includes the inhibition of translation to prevent further accumulation of unfolded proteins, the increased expression of proteins involved in polypeptide folding, known as the unfolded protein response (UPR), and the destruction of misfolded proteins by the ER-associated protein degradation (ERAD) system. This gene may play a role in both UPR and ERAD. Its expression is induced by UPR and it has an ER stress response element in its promoter region while the encoded protein has an N-terminal ubiquitin-like domain which may interact with the ERAD system. This protein has been shown to interact with presenilin proteins and to increase the level of amyloid-beta protein following its overexpression. Alternative splicing of this gene produces multiple transcript variants encoding different isoforms. The full-length nature of all transcript variants has not been determined. [provided by RefSeq, Jan 2013]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001436352.1. 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
	HERPUD1	NM_014685.4	MANE Select	c.283_285delCCAinsGCT	p.Pro95Ala	missense	N/A	NP_055500.1	Q15011-1
	HERPUD1	NM_001436352.1		c.83_85delCCAinsGCT	p.AlaArg28*	stop_gained	N/A	NP_001423281.1
	HERPUD1	NM_001010989.3		c.280_282delCCAinsGCT	p.Pro94Ala	missense	N/A	NP_001010989.1	Q15011-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HERPUD1	ENST00000439977.7	TSL:1 MANE Select	c.283_285delCCAinsGCT	p.Pro95Ala	missense	N/A	ENSP00000409555.2	Q15011-1
	HERPUD1	ENST00000300302.9	TSL:1	c.280_282delCCAinsGCT	p.Pro94Ala	missense	N/A	ENSP00000300302.5	Q15011-2
	HERPUD1	ENST00000344114.8	TSL:1	c.280_282delCCAinsGCT	p.Pro94Ala	missense	N/A	ENSP00000340931.4	Q15011-3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-56969370;