rs6104

chr18-63903295-C-Achr18-63903295-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002575.3(SERPINB2):c.1238C>A(p.Ser413Tyr) 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. 13/21 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. S413C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SERPINB2 NM_002575.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.933

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09064734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB2	NM_002575.3	c.1238C>A	p.Ser413Tyr	missense_variant	8/8	ENST00000299502.9
SERPINB2	NM_001143818.2	c.1238C>A	p.Ser413Tyr	missense_variant	9/9
SERPINB2	XM_024451192.2	c.1238C>A	p.Ser413Tyr	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB2	ENST00000299502.9	c.1238C>A	p.Ser413Tyr	missense_variant	8/8	1	NM_002575.3	P1
SERPINB2	ENST00000457692.5	c.1238C>A	p.Ser413Tyr	missense_variant	9/9	5		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1376336 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 675540

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	17
Dann	Uncertain	0.98
DEOGEN2	Benign	0.34	T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.31	N
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.091	T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	0.94	P;P
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.12
Sift	Benign	0.071	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.080	B;B
Vest4		0.14
MutPred		0.28		Loss of disorder (P = 0.0182);Loss of disorder (P = 0.0182);
MVP		0.58
MPC		0.092
ClinPred		0.51	D
GERP RS		1.3
Varity_R		0.32
gMVP		0.19

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: rs6104; hg19: chr18-61570529;