Genetic Variant NM_001370475.1:c.152A>T (chr18-63710345-A-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_001370475.1(SERPINB11):c.152A>T(p.Glu51Val) 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. 13/19 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. E51K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SERPINB11
NM_001370475.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.694

Publications

28 publications found

Variant links:

Genes affected

SERPINB11 (HGNC:14221): (serpin family B member 11) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in cytoplasm. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SERPINB11 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=0.20685422).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370475.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINB11	NM_001370475.1	MANE Select	c.152A>T	p.Glu51Val	missense	Exon 2 of 8	NP_001357404.1	F5GYW9
SERPINB11	NM_080475.5		c.152A>T	p.Glu51Val	missense	Exon 3 of 9	NP_536723.2	Q96P15-1
SERPINB11	NM_001291278.2		c.152A>T	p.Glu51Val	missense	Exon 2 of 6	NP_001278207.1	A0A096LPD5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINB11	ENST00000544088.6	TSL:2 MANE Select	c.152A>T	p.Glu51Val	missense	Exon 2 of 8	ENSP00000441497.1	F5GYW9
SERPINB11	ENST00000382749.9	TSL:1	c.152A>T	p.Glu51Val	missense	Exon 3 of 9	ENSP00000421854.1	Q96P15-1
SERPINB11	ENST00000623262.3	TSL:1	c.152A>T	p.Glu51Val	missense	Exon 1 of 5	ENSP00000485532.1	Q96P15-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460064

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726316

African (AFR)

AF:

0.00

AC:

AN:

33382

American (AMR)

AF:

0.00

AC:

AN:

44506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26036

East Asian (EAS)

AF:

0.00

AC:

AN:

39640

South Asian (SAS)

AF:

0.00

AC:

AN:

85914

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111158

Other (OTH)

AF:

0.00

AC:

AN:

60300

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Benign

-0.12

CADD

Benign

(source)

DANN

Benign

0.94

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.31

M_CAP

Benign

0.023

MetaRNN

Benign

0.21

MetaSVM

Uncertain

0.15

PhyloP100

0.69

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.53

REVEL

Uncertain

0.31

Sift4G

Benign

0.15

Vest4

0.16

MutPred

0.50

Loss of solvent accessibility (P = 0.0052)

MVP

0.45

MPC

0.013

ClinPred

0.95

GERP RS

4.3

PromoterAI

-0.025

Neutral

(source)

gMVP

0.56

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over