Variant 18-63655750-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006919.3(SERPINB3):c.1080T>A(p.Asn360Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,613,728 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

SERPINB3
NM_006919.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.57

Variant links:

Genes affected

SERPINB3 (HGNC:10569): (serpin family B member 3) Enables cysteine-type endopeptidase inhibitor activity; protease binding activity; and virus receptor activity. Involved in several processes, including autocrine signaling; paracrine signaling; and regulation of cellular protein metabolic process. Located in cytoplasmic vesicle; extracellular exosome; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SERPINB3 links:

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0354563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB3	NM_006919.3 linkuse as main transcript	c.1080T>A	p.Asn360Lys	missense_variant	8/8	ENST00000283752.10	NP_008850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINB3	ENST00000283752.10 linkuse as main transcript	c.1080T>A	p.Asn360Lys	missense_variant	8/8	1	NM_006919.3	ENSP00000283752	P1	P29508-1
SERPINB3	ENST00000332821.8 linkuse as main transcript	c.924T>A	p.Asn308Lys	missense_variant	7/7	1		ENSP00000329498		P29508-2
SERPINB11	ENST00000489748.5 linkuse as main transcript	c.-242A>T		5_prime_UTR_variant	2/7	2		ENSP00000480275

Frequencies

GnomAD3 genomes

AF:

0.000165

AC:

AN:

151974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000557

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.0000717

AC:

AN:

251078

Hom.:

AF XY:

0.0000590

AC XY:

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.000867

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461754

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000165

AC:

AN:

151974

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.000557

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000178

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 22, 2023

The c.1080T>A (p.N360K) alteration is located in exon 8 (coding exon 7) of the SERPINB3 gene. This alteration results from a T to A substitution at nucleotide position 1080, causing the asparagine (N) at amino acid position 360 to be replaced by a lysine (K). 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

0.12

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.0030

DANN

Benign

0.85

DEOGEN2

Benign

0.085

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.27

T;T

M_CAP

Benign

0.052

MetaRNN

Benign

0.035

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.18

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.94

N;N

REVEL

Benign

0.20

Sift

Benign

0.29

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.034

B;B

Vest4

0.079

MutPred

0.46

Gain of methylation at N360 (P = 0.0114);.;

MVP

0.37

MPC

0.027

ClinPred

0.0099

GERP RS

-1.3

Varity_R

0.23

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over