18-63891538-C-T

Variant names:

• chr18-63891538-C-T
• NM_002575.3:c.94C>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_002575.3(SERPINB2):​c.94C>T​(p.Pro32Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERPINB2 NM_002575.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.55
• Publications: 0 publications found

Genes affected

SERPINB2 (HGNC:8584): (serpin family B member 2) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

LOC124904356 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.98

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB2	NM_002575.3	c.94C>T	p.Pro32Ser	missense_variant	Exon 2 of 8	ENST00000299502.9	NP_002566.1
SERPINB2	NM_001143818.2	c.94C>T	p.Pro32Ser	missense_variant	Exon 3 of 9		NP_001137290.1
SERPINB2	XM_024451192.2	c.94C>T	p.Pro32Ser	missense_variant	Exon 2 of 8		XP_024306960.1
LOC124904356	XR_007066466.1	n.183+1083G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB2	ENST00000299502.9	c.94C>T	p.Pro32Ser	missense_variant	Exon 2 of 8	1	NM_002575.3	ENSP00000299502.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.94C>T (p.P32S) alteration is located in exon 3 (coding exon 1) of the SERPINB2 gene. This alteration results from a C to T substitution at nucleotide position 94, causing the proline (P) at amino acid position 32 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.55
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.63	D;D;D;D;D
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.91	D;.;D;D;D
M_CAP	Pathogenic	0.31	D
MetaRNN	Pathogenic	0.98	D;D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.1	.;M;M;.;.
PhyloP100		6.5
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-7.9	D;D;D;D;D
REVEL	Pathogenic	0.82
Sift	Pathogenic	0.0	D;T;T;T;D
Sift4G	Pathogenic	0.0	D;D;D;D;T
Polyphen		1.0	.;D;D;.;.
Vest4		0.92, 0.91
MutPred		0.89		Loss of glycosylation at P32 (P = 0.0668);Loss of glycosylation at P32 (P = 0.0668);Loss of glycosylation at P32 (P = 0.0668);Loss of glycosylation at P32 (P = 0.0668);Loss of glycosylation at P32 (P = 0.0668);
MVP		0.98
MPC		0.12
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.78
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr18-61558772;