chr18-63979936-CCA-AGC

Variant names:

• chr18-63979936-CCA-AGC
• ENST00000397985.7:c.293_295delCCAinsAGC

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1

The ENST00000397985.7(SERPINB8):​c.293_295delCCAinsAGC​(p.CysAsp98*) 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. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERPINB8 ENST00000397985.7 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547
• Publications: 0 publications found

Genes affected

SERPINB8 (HGNC:8952): (serpin family B member 8) The protein encoded by this gene is a member of the ov-serpin family of serine protease inhibitors. The encoded protein is produced by platelets and can bind to and inhibit the function of furin, a serine protease involved in platelet functions. In addition, this protein has been found to enhance the mechanical stability of cell-cell adhesion in the skin, and defects in this gene have been associated with an autosomal-recessive form of exfoliative ichthyosis. [provided by RefSeq, Jan 2017]

HMSD (HGNC:23037): (histocompatibility minor serpin domain containing) This gene encodes a serpin-domain containing protein that may function as a serine protease inhibitor. This gene is primarily expressed in cells of myeloid lineage. A polymorphism in this gene may result in the expression a splice variant that encodes a minor histocompatibility antigen. [provided by RefSeq, Oct 2010]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397985.7. 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
	SERPINB8	NM_002640.4	MANE Select	c.304_306delCCAinsAGC	p.Pro102Ser	missense splice_region	N/A	NP_002631.3
	SERPINB8	NM_001366198.1		c.304_306delCCAinsAGC	p.Pro102Ser	missense splice_region	N/A	NP_001353127.1	P50452-1
	SERPINB8	NM_198833.2		c.304_306delCCAinsAGC	p.Pro102Ser	missense splice_region	N/A	NP_942130.1	P50452-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB8	ENST00000397985.7	TSL:1 MANE Select	c.293_295delCCAinsAGC	p.CysAsp98*	stop_gained	N/A	ENSP00000381072.2	P50452-1
	SERPINB8	ENST00000397988.7	TSL:1	c.293_295delCCAinsAGC	p.CysAsp98*	stop_gained	N/A	ENSP00000381075.3	P50452-2
	SERPINB8	ENST00000353706.6	TSL:5	c.293_295delCCAinsAGC	p.CysAsp98*	stop_gained	N/A	ENSP00000331368.3	P50452-1

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		0.55

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: chr18-61647170;