Variant 18-63493075-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002639.5(SERPINB5):c.547T>C(p.Cys183Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000617 in 1,614,178 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00063 ( 0 hom. )

Consequence

SERPINB5
NM_002639.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02

Variant links:

Genes affected

SERPINB5 (HGNC:8949): (serpin family B member 5) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to act upstream of or within several processes, including extracellular matrix organization; prostate gland morphogenesis; and regulation of epithelial cell proliferation. Located in cytoplasm. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

SERPINB5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030227125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB5	NM_002639.5 linkuse as main transcript	c.547T>C	p.Cys183Arg	missense_variant	5/7	ENST00000382771.9	NP_002630.2	P36952-1A0A024R2B6
SERPINB5	XM_006722483.4 linkuse as main transcript	c.34T>C	p.Cys12Arg	missense_variant	2/4		XP_006722546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SERPINB5	ENST00000382771.9 linkuse as main transcript	c.547T>C	p.Cys183Arg	missense_variant	5/7	1	NM_002639.5	ENSP00000372221.4	P36952-1
SERPINB5	ENST00000489441.5 linkuse as main transcript	c.547T>C	p.Cys183Arg	missense_variant	5/5	1		ENSP00000467158.1	P36952-2
SERPINB5	ENST00000464346.1 linkuse as main transcript	n.229T>C		non_coding_transcript_exon_variant	2/4	3
SERPINB5	ENST00000465652.5 linkuse as main transcript	n.220T>C		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000529

AC:

133

AN:

251446

Hom.:

AF XY:

0.000537

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.000694

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000800

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000633

AC:

926

AN:

1461864

Hom.:

Cov.:

AF XY:

0.000659

AC XY:

479

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000638

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000683

Gnomad4 OTH exome

AF:

0.000695

GnomAD4 genome

AF:

0.000460

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000862

Hom.:

Bravo

AF:

0.000578

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000576

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00153

EpiControl

AF:

0.00184

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

Sep 01, 2021

The c.547T>C (p.C183R) alteration is located in exon 5 (coding exon 4) of the SERPINB5 gene. This alteration results from a T to C substitution at nucleotide position 547, causing the cysteine (C) at amino acid position 183 to be replaced by an arginine (R). 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

0.17

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.19

T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.030

T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.95

L;L

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.7

N;.

REVEL

Benign

0.21

Sift

Benign

0.51

T;.

Sift4G

Benign

0.56

T;D

Polyphen

0.0040

B;B

Vest4

0.29

MVP

0.65

MPC

0.10

ClinPred

0.0098

GERP RS

3.7

Varity_R

0.32

gMVP

0.84

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