Variant 18-63639756-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002974.4(SERPINB4):c.490C>A(p.Pro164Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000087 in 1,609,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

SERPINB4
NM_002974.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.775

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22490197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB4	NM_002974.4 linkuse as main transcript	c.490C>A	p.Pro164Thr	missense_variant	6/8	ENST00000341074.10	NP_002965.1
SERPINB4	NM_175041.2 linkuse as main transcript	c.490C>A	p.Pro164Thr	missense_variant	6/8		NP_778206.1
SERPINB4	XM_011526138.2 linkuse as main transcript	c.490C>A	p.Pro164Thr	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.490C>A	p.Pro164Thr	missense_variant	6/8	1	NM_002974.4	ENSP00000343445.5	P48594
SERPINB4	ENST00000413673.5 linkuse as main transcript	c.493C>A	p.Pro165Thr	missense_variant	5/7	1		ENSP00000398645.1	H0Y5H9
SERPINB4	ENST00000436264.1 linkuse as main transcript	c.361C>A	p.Pro121Thr	missense_variant	5/6	5		ENSP00000399796.1	C9JZ65

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152054

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:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000401

AC:

AN:

249412

Hom.:

AF XY:

0.0000371

AC XY:

AN XY:

134752

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000492

Gnomad SAS exome

AF:

0.0000331

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000755

AC:

AN:

1457892

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.0000351

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152054

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000330

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

May 31, 2023

The c.490C>A (p.P164T) alteration is located in exon 6 (coding exon 5) of the SERPINB4 gene. This alteration results from a C to A substitution at nucleotide position 490, causing the proline (P) at amino acid position 164 to be replaced by a threonine (T). 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

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

T;.

Eigen

Benign

0.13

Eigen_PC

Benign

-0.079

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.22

T;T

MetaSVM

Uncertain

-0.16

MutationAssessor

Uncertain

2.4

M;.

PROVEAN

Pathogenic

-6.5

D;D

REVEL

Uncertain

0.29

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.0090

D;.

Polyphen

1.0

D;.

Vest4

0.12

MutPred

0.42

Loss of ubiquitination at K160 (P = 0.0648);.;

MVP

0.57

MPC

0.050

ClinPred

0.45

GERP RS

3.4

Varity_R

0.20

gMVP

0.22

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