Variant 18-63639714-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002974.4(SERPINB4):c.532A>C(p.Asn178His) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,612,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SERPINB4
NM_002974.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17

Variant links:

Genes affected

SERPINB4 (HGNC:10570): (serpin family B member 4) The protein encoded by this gene is a member of the serpin family of serine protease inhibitors. The encoded protein is highly expressed in many tumor cells and can inactivate granzyme M, an enzyme that kills tumor cells. This protein, along with serpin B3, can be processed into smaller fragments that aggregate to form an autoantigen in psoriasis, probably by causing chronic inflammation. [provided by RefSeq, Jan 2017]

SERPINB4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.868

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB4	NM_002974.4 linkuse as main transcript	c.532A>C	p.Asn178His	missense_variant	6/8	ENST00000341074.10	NP_002965.1
SERPINB4	NM_175041.2 linkuse as main transcript	c.532A>C	p.Asn178His	missense_variant	6/8		NP_778206.1
SERPINB4	XM_011526138.2 linkuse as main transcript	c.532A>C	p.Asn178His	missense_variant	6/8		XP_011524440.1	P48594

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SERPINB4	ENST00000341074.10 linkuse as main transcript	c.532A>C	p.Asn178His	missense_variant	6/8	1	NM_002974.4	ENSP00000343445.5	P48594
SERPINB4	ENST00000413673.5 linkuse as main transcript	c.535A>C	p.Asn179His	missense_variant	5/7	1		ENSP00000398645.1	H0Y5H9
SERPINB4	ENST00000436264.1 linkuse as main transcript	c.403A>C	p.Asn135His	missense_variant	5/6	5		ENSP00000399796.1	C9JZ65

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250844

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135582

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1459910

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726358

show subpopulations

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:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000227

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 02, 2022

The c.532A>C (p.N178H) alteration is located in exon 6 (coding exon 5) of the SERPINB4 gene. This alteration results from a A to C substitution at nucleotide position 532, causing the asparagine (N) at amino acid position 178 to be replaced by a histidine (H). 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

Pathogenic

0.69

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.72

D;.

Eigen

Uncertain

0.29

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.024

MetaRNN

Pathogenic

0.87

D;D

MetaSVM

Uncertain

0.48

MutationAssessor

Pathogenic

4.9

H;.

PROVEAN

Pathogenic

-4.8

D;D

REVEL

Uncertain

0.53

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0

D;.

Polyphen

1.0

D;.

Vest4

0.64

MVP

0.69

MPC

0.063

ClinPred

1.0

GERP RS

3.1

Varity_R

0.46

gMVP

0.66

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