18-63639761-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_002974.4(SERPINB4):ā€‹c.485T>Cā€‹(p.Leu162Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,609,956 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000079 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000069 ( 0 hom. )

Consequence

SERPINB4
NM_002974.4 missense

Scores

7
5
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.758

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SERPINB4NM_002974.4 linkuse as main transcriptc.485T>C p.Leu162Pro missense_variant 6/8 ENST00000341074.10
SERPINB4NM_175041.2 linkuse as main transcriptc.485T>C p.Leu162Pro missense_variant 6/8
SERPINB4XM_011526138.2 linkuse as main transcriptc.485T>C p.Leu162Pro missense_variant 6/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SERPINB4ENST00000341074.10 linkuse as main transcriptc.485T>C p.Leu162Pro missense_variant 6/81 NM_002974.4 P1
SERPINB4ENST00000413673.5 linkuse as main transcriptc.491T>C p.Leu164Pro missense_variant 5/71
SERPINB4ENST00000436264.1 linkuse as main transcriptc.356T>C p.Leu119Pro missense_variant 5/65

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152144
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000290
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000562
AC:
14
AN:
249198
Hom.:
0
AF XY:
0.0000446
AC XY:
6
AN XY:
134636
show subpopulations
Gnomad AFR exome
AF:
0.000803
Gnomad AMR exome
AF:
0.0000294
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:
0.00000686
AC:
10
AN:
1457812
Hom.:
0
Cov.:
30
AF XY:
0.00000414
AC XY:
3
AN XY:
725186
show subpopulations
Gnomad4 AFR exome
AF:
0.000241
Gnomad4 AMR exome
AF:
0.0000227
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000789
AC:
12
AN:
152144
Hom.:
0
Cov.:
32
AF XY:
0.0000942
AC XY:
7
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.000290
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000119
Hom.:
0
Bravo
AF:
0.000128
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000659
AC:
8

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 submitterclinical testingAmbry GeneticsApr 07, 2022The c.485T>C (p.L162P) alteration is located in exon 6 (coding exon 5) of the SERPINB4 gene. This alteration results from a T to C substitution at nucleotide position 485, causing the leucine (L) at amino acid position 162 to be replaced by a proline (P). 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
0.77
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Pathogenic
0.31
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.57
D;.
Eigen
Benign
0.14
Eigen_PC
Benign
-0.062
FATHMM_MKL
Benign
0.64
D
LIST_S2
Benign
0.64
T;T
M_CAP
Benign
0.016
T
MetaRNN
Pathogenic
0.76
D;D
MetaSVM
Uncertain
0.61
D
MutationAssessor
Pathogenic
3.7
H;.
MutationTaster
Benign
1.0
D;D
PROVEAN
Pathogenic
-6.0
D;D
REVEL
Pathogenic
0.69
Sift
Uncertain
0.010
D;D
Sift4G
Pathogenic
0.0
D;.
Polyphen
1.0
D;.
Vest4
0.81
MVP
0.60
MPC
0.056
ClinPred
0.55
D
GERP RS
4.3
Varity_R
0.76
gMVP
0.64

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.

Other links and lift over

dbSNP: rs145104474; hg19: chr18-61306995; API