18-63792442-AG-TAAACTTTACCT

Position:

• chr18-63792442-AG-TAAACTTTACCT

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The ENST00000398019.7(SERPINB7):​c.205_206delAGinsTAAACTTTACCT​(p.Ser69fs) variant causes a frameshift, stop gained, missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S69P) has been classified as Uncertain significance. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERPINB7 ENST00000398019.7 frameshift, stop_gained, missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.37

Genes affected

SERPINB7 (HGNC:13902): (serpin family B member 7) This gene encodes a member of a family of proteins which function as protease inhibitors. Expression of this gene is upregulated in IgA nephropathy and mutations have been found to cause palmoplantar keratoderma, Nagashima type. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 18-63792442-AG-TAAACTTTACCT is Pathogenic according to our data. Variant chr18-63792442-AG-TAAACTTTACCT is described in ClinVar as [Pathogenic]. Clinvar id is 102447.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB7	NM_003784.4	c.218_219delAGinsTAAACTTTACCT	p.Gln73delinsLeuAsnPheThr???	missense_variant, splice_region_variant		ENST00000398019.7	NP_003775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINB7	ENST00000398019.7	c.205_206delAGinsTAAACTTTACCT	p.Ser69fs	frameshift_variant, stop_gained, missense_variant	3/8	1	NM_003784.4	ENSP00000381101.2

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

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Palmoplantar keratoderma, Nagashima type Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 01, 2014

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs797044479; hg19: chr18-61459676;