Genetic Variant NM_002575.3:c.1238C>T (chr18-63903295-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002575.3(SERPINB2):c.1238C>T(p.Ser413Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,376,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

SERPINB2
NM_002575.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.933

Publications

0 publications found

Variant links:

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]

SERPINB2 links:

ENSG00000289724 (HGNC:):

ENSG00000289724 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15231907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB2	NM_002575.3 link	c.1238C>T	p.Ser413Phe	missense_variant	Exon 8 of 8	ENST00000299502.9	NP_002566.1	P05120
SERPINB2	NM_001143818.2 link	c.1238C>T	p.Ser413Phe	missense_variant	Exon 9 of 9		NP_001137290.1	P05120
SERPINB2	XM_024451192.2 link	c.1238C>T	p.Ser413Phe	missense_variant	Exon 8 of 8		XP_024306960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SERPINB2	ENST00000299502.9 link	c.1238C>T	p.Ser413Phe	missense_variant	Exon 8 of 8	1	NM_002575.3	ENSP00000299502.4	P05120
ENSG00000289724	ENST00000418725.1 link	c.546+320C>T		intron_variant	Intron 5 of 6	5		ENSP00000392381.1	H7C004
SERPINB2	ENST00000457692.5 link	c.1238C>T	p.Ser413Phe	missense_variant	Exon 9 of 9	5		ENSP00000401645.1	P05120
ENSG00000289724	ENST00000397996.6 link	c.546+320C>T		intron_variant	Intron 5 of 7	5		ENSP00000381082.2	H7BYS2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.27e-7

AC:

AN:

1376336

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

675540

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30520

American (AMR)

AF:

0.00

AC:

AN:

31784

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20844

East Asian (EAS)

AF:

0.0000259

AC:

AN:

38624

South Asian (SAS)

AF:

0.00

AC:

AN:

71584

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5346

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1070350

Other (OTH)

AF:

0.00

AC:

AN:

56682

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.26

LIST_S2

Uncertain

0.95

.;D

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.15

T;T

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.5

M;M

PhyloP100

0.93

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.24

Sift

Uncertain

0.0030

D;D

Sift4G

Benign

0.11

T;T

Polyphen

0.63

P;P

Vest4

0.14

MutPred

0.31

Loss of disorder (P = 0.011);Loss of disorder (P = 0.011);

MVP

0.64

MPC

0.071

ClinPred

0.85

GERP RS

1.3

Varity_R

0.46

gMVP

0.18

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over