18-63897751-T-C

Variant summary

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

The NM_002575.3(SERPINB2):ā€‹c.442T>Cā€‹(p.Tyr148His) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,459,002 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: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

SERPINB2
NM_002575.3 missense

Scores

4
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.63
Variant links:
Genes affected
SERPINB2 (HGNC:8584): (serpin family B member 2) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in extracellular region and plasma membrane. 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 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, 0.753

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SERPINB2NM_002575.3 linkuse as main transcriptc.442T>C p.Tyr148His missense_variant 5/8 ENST00000299502.9
SERPINB2NM_001143818.2 linkuse as main transcriptc.442T>C p.Tyr148His missense_variant 6/9
SERPINB2XM_024451192.2 linkuse as main transcriptc.442T>C p.Tyr148His missense_variant 5/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SERPINB2ENST00000299502.9 linkuse as main transcriptc.442T>C p.Tyr148His missense_variant 5/81 NM_002575.3 P1
SERPINB2ENST00000457692.5 linkuse as main transcriptc.442T>C p.Tyr148His missense_variant 6/95 P1
SERPINB2ENST00000413956.5 linkuse as main transcriptc.442T>C p.Tyr148His missense_variant 6/65
SERPINB2ENST00000482254.1 linkuse as main transcriptn.398T>C non_coding_transcript_exon_variant 4/65

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250882
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135630
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1459002
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
726054
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.00000824
AC:
1

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 GeneticsJun 21, 2021The c.442T>C (p.Y148H) alteration is located in exon 6 (coding exon 4) of the SERPINB2 gene. This alteration results from a T to C substitution at nucleotide position 442, causing the tyrosine (Y) at amino acid position 148 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
Benign
0.21
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Pathogenic
0.23
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.36
T;T;T
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.61
.;T;T
M_CAP
Benign
0.076
D
MetaRNN
Pathogenic
0.75
D;D;D
MetaSVM
Uncertain
0.45
D
MutationAssessor
Benign
1.9
M;M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-3.8
D;D;D
REVEL
Pathogenic
0.78
Sift
Benign
0.063
T;T;D
Sift4G
Benign
0.12
T;T;D
Polyphen
1.0
D;D;.
Vest4
0.49
MVP
0.67
MPC
0.13
ClinPred
0.96
D
GERP RS
5.6
Varity_R
0.77
gMVP
0.52

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: rs751668373; hg19: chr18-61564985; API