18-63639754-AGG-TGA

Variant names:

• chr18-63639754-AGG-TGA
• NM_002974.4:c.490_492delCCTinsTCA
• SERPINB4 p.Pro164Ser

Variant summary

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

The NM_002974.4(SERPINB4):​c.490_492delCCTinsTCA​(p.Pro164Ser) variant causes a missense 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P164T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERPINB4 NM_002974.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.559
• Publications: 0 publications found

Genes affected

SERPINB4 (HGNC:10570): (serpin family B member 4) The protein encoded by this gene is a member of the serpin family of serine protease inhibitors. The encoded protein is highly expressed in many tumor cells and can inactivate granzyme M, an enzyme that kills tumor cells. This protein, along with serpin B3, can be processed into smaller fragments that aggregate to form an autoantigen in psoriasis, probably by causing chronic inflammation. [provided by RefSeq, Jan 2017]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002974.4. 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
	SERPINB4	NM_002974.4	MANE Select	c.490_492delCCTinsTCA	p.Pro164Ser	missense	N/A	NP_002965.1	P48594
	SERPINB4	NM_175041.2		c.490_492delCCTinsTCA	p.Pro164Ser	missense	N/A	NP_778206.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB4	ENST00000341074.10	TSL:1 MANE Select	c.490_492delCCTinsTCA	p.Pro164Ser	missense	N/A	ENSP00000343445.5	P48594
	SERPINB4	ENST00000413673.5	TSL:1	c.493_495delCCTinsTCA	p.Pro165Ser	missense	N/A	ENSP00000398645.1	H0Y5H9
	SERPINB4	ENST00000436264.1	TSL:5	c.361_363delCCTinsTCA	p.Pro121Ser	missense	N/A	ENSP00000399796.1	C9JZ65

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		0.56

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: chr18-61306988;