NM_002575.3:c.124G>A

Variant names:

• chr18-63891568-G-A
• NM_002575.3:c.124G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002575.3(SERPINB2):​c.124G>A​(p.Val42Ile) 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. 16/21 in silico tools predict a benign 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: 2.02

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29205877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB2	NM_002575.3	c.124G>A	p.Val42Ile	missense_variant	Exon 2 of 8	ENST00000299502.9	NP_002566.1
SERPINB2	NM_001143818.2	c.124G>A	p.Val42Ile	missense_variant	Exon 3 of 9		NP_001137290.1
SERPINB2	XM_024451192.2	c.124G>A	p.Val42Ile	missense_variant	Exon 2 of 8		XP_024306960.1
LOC124904356	XR_007066466.1	n.183+1053C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB2	ENST00000299502.9	c.124G>A	p.Val42Ile	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

Feb 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.124G>A (p.V42I) alteration is located in exon 3 (coding exon 1) of the SERPINB2 gene. This alteration results from a G to A substitution at nucleotide position 124, causing the valine (V) at amino acid position 42 to be replaced by an isoleucine (I). 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	Benign	0.091
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.10	T;T;T;T;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.79	T;.;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.29	T;T;T;T;T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.6	.;L;L;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.67	N;N;N;N;N
REVEL	Benign	0.26
Sift	Benign	0.072	T;T;T;D;T
Sift4G	Benign	0.18	T;T;T;T;T
Polyphen		0.015	.;B;B;.;.
Vest4		0.18, 0.19
MutPred		0.56		Loss of glycosylation at S46 (P = 0.1202);Loss of glycosylation at S46 (P = 0.1202);Loss of glycosylation at S46 (P = 0.1202);Loss of glycosylation at S46 (P = 0.1202);Loss of glycosylation at S46 (P = 0.1202);
MVP		0.55
MPC		0.019
ClinPred		0.12	T
GERP RS		0.54
Varity_R		0.30
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-61558802;