chr18-63655746-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_006919.3(SERPINB3):c.1084G>A(p.Glu362Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00694 in 1,613,880 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0046 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0072 ( 52 hom. )
Consequence
SERPINB3
NM_006919.3 missense
NM_006919.3 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: -1.75
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]
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.007921547).
BP6
?
Variant 18-63655746-C-T is Benign according to our data. Variant chr18-63655746-C-T is described in ClinVar as [Benign]. Clinvar id is 774727.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAd at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINB3 | NM_006919.3 | c.1084G>A | p.Glu362Lys | missense_variant | 8/8 | ENST00000283752.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINB3 | ENST00000283752.10 | c.1084G>A | p.Glu362Lys | missense_variant | 8/8 | 1 | NM_006919.3 | P1 | |
SERPINB3 | ENST00000332821.8 | c.928G>A | p.Glu310Lys | missense_variant | 7/7 | 1 | |||
SERPINB11 | ENST00000489748.5 | c.-246C>T | 5_prime_UTR_variant | 2/7 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00459 AC: 698AN: 152010Hom.: 2 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
698
AN:
152010
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00586 AC: 1471AN: 251080Hom.: 8 AF XY: 0.00611 AC XY: 829AN XY: 135686
GnomAD3 exomes
AF:
AC:
1471
AN:
251080
Hom.:
AF XY:
AC XY:
829
AN XY:
135686
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00718 AC: 10500AN: 1461752Hom.: 52 Cov.: 31 AF XY: 0.00713 AC XY: 5184AN XY: 727178
GnomAD4 exome
AF:
AC:
10500
AN:
1461752
Hom.:
Cov.:
31
AF XY:
AC XY:
5184
AN XY:
727178
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00459 AC: 698AN: 152128Hom.: 2 Cov.: 32 AF XY: 0.00440 AC XY: 327AN XY: 74374
GnomAD4 genome
?
AF:
AC:
698
AN:
152128
Hom.:
Cov.:
32
AF XY:
AC XY:
327
AN XY:
74374
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
29
ALSPAC
AF:
AC:
34
ESP6500AA
AF:
AC:
8
ESP6500EA
AF:
AC:
70
ExAC
?
AF:
AC:
798
Asia WGS
AF:
AC:
7
AN:
3476
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 18, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at