Variant 18-63486947-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002639.5(SERPINB5):c.170T>G(p.Val57Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

SERPINB5
NM_002639.5 missense, splice_region

Scores

Splicing: ADA: 0.03080

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19807309).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB5	NM_002639.5 linkuse as main transcript	c.170T>G	p.Val57Gly	missense_variant, splice_region_variant	3/7	ENST00000382771.9	NP_002630.2	P36952-1A0A024R2B6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SERPINB5	ENST00000382771.9 linkuse as main transcript	c.170T>G	p.Val57Gly	missense_variant, splice_region_variant	3/7	1	NM_002639.5	ENSP00000372221.4	P36952-1
SERPINB5	ENST00000489441.5 linkuse as main transcript	c.170T>G	p.Val57Gly	missense_variant, splice_region_variant	3/5	1		ENSP00000467158.1	P36952-2
SERPINB5	ENST00000424602.1 linkuse as main transcript	c.170T>G	p.Val57Gly	missense_variant, splice_region_variant	3/4	4		ENSP00000408821.1	C9JLM5
SERPINB5	ENST00000588986.1 linkuse as main transcript	n.271T>G		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251178

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.000123

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:

0.0000704

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461718

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727162

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:

0.0000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000100

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

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

Jan 30, 2024

The c.170T>G (p.V57G) alteration is located in exon 3 (coding exon 2) of the SERPINB5 gene. This alteration results from a T to G substitution at nucleotide position 170, causing the valine (V) at amino acid position 57 to be replaced by a glycine (G). 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

Benign

-0.0021

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.60

D;.;T

Eigen

Benign

0.0043

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.46

T;T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Uncertain

-0.083

MutationAssessor

Benign

1.6

L;L;.

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.0

D;.;N

REVEL

Uncertain

0.64

Sift

Benign

0.14

T;.;T

Sift4G

Benign

0.12

T;T;T

Polyphen

0.15

B;B;.

Vest4

0.52

MVP

0.96

MPC

0.086

ClinPred

0.056

GERP RS

5.2

Varity_R

0.53

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.031

dbscSNV1_RF

Benign

0.056

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