Variant 18-63499268-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002639.5(SERPINB5):c.716A>T(p.Glu239Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000014 in 1,433,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

SERPINB5
NM_002639.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.88

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28366023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB5	NM_002639.5 linkuse as main transcript	c.716A>T	p.Glu239Val	missense_variant	6/7	ENST00000382771.9	NP_002630.2	P36952-1A0A024R2B6
SERPINB5	XM_006722483.4 linkuse as main transcript	c.203A>T	p.Glu68Val	missense_variant	3/4		XP_006722546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SERPINB5	ENST00000382771.9 linkuse as main transcript	c.716A>T	p.Glu239Val	missense_variant	6/7	1	NM_002639.5	ENSP00000372221.4	P36952-1
SERPINB5	ENST00000464346.1 linkuse as main transcript	n.398A>T		non_coding_transcript_exon_variant	3/4	3
SERPINB5	ENST00000465652.5 linkuse as main transcript	n.389A>T		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000216

AC:

AN:

231922

Hom.:

AF XY:

0.0000318

AC XY:

AN XY:

125666

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000470

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000140

AC:

AN:

1433630

Hom.:

Cov.:

AF XY:

0.0000196

AC XY:

AN XY:

712570

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:

0.0000155

Gnomad4 OTH exome

AF:

0.0000506

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

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

Oct 17, 2023

The c.716A>T (p.E239V) alteration is located in exon 6 (coding exon 5) of the SERPINB5 gene. This alteration results from a A to T substitution at nucleotide position 716, causing the glutamic acid (E) at amino acid position 239 to be replaced by a valine (V). 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

0.15

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Uncertain

0.51

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.55

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.81

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.41

MutationAssessor

Benign

0.81

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.36

Sift

Uncertain

0.023

Sift4G

Benign

0.21

Polyphen

0.0080

Vest4

0.34

MVP

0.81

MPC

0.074

ClinPred

0.24

GERP RS

-0.068

Varity_R

0.29

gMVP

0.66

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