rs2289520

Positions:

• chr18-63493087-G-A
• chr18-63493087-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002639.5(SERPINB5):​c.559G>A​(p.Val187Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. V187L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERPINB5 NM_002639.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330

Genes affected

SERPINB5 (HGNC:8949): (serpin family B member 5) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to act upstream of or within several processes, including extracellular matrix organization; prostate gland morphogenesis; and regulation of epithelial cell proliferation. Located in cytoplasm. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04249561).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB5	NM_002639.5	c.559G>A	p.Val187Ile	missense_variant	5/7	ENST00000382771.9
SERPINB5	XM_006722483.4	c.46G>A	p.Val16Ile	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB5	ENST00000382771.9	c.559G>A	p.Val187Ile	missense_variant	5/7	1	NM_002639.5	P1
SERPINB5	ENST00000489441.5	c.559G>A	p.Val187Ile	missense_variant	5/5	1
SERPINB5	ENST00000464346.1	n.241G>A		non_coding_transcript_exon_variant	2/4	3
SERPINB5	ENST00000465652.5	n.232G>A		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 32

Alfa AF: 0.00000862 Hom.: 1126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.71
DEOGEN2	Benign	0.17	T;.
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.042	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.63	N;N
MutationTaster	Benign	0.94	P;P
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.77	N;.
REVEL	Benign	0.043
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.075
MutPred		0.44		Gain of ubiquitination at K189 (P = 0.0686);Gain of ubiquitination at K189 (P = 0.0686);
MVP		0.17
MPC		0.050
ClinPred		0.069	T
GERP RS		0.34
Varity_R		0.11
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2289520; hg19: chr18-61160320;