dbSNP rs17090921: SERPINA9:p.Pro218Leu (chr14-94467358-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_175739.4(SERPINA9):c.653C>T(p.Pro218Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,610,776 control chromosomes in the GnomAD database, including 78,596 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.28 ( 6444 hom., cov: 33)

Exomes 𝑓: 0.31 ( 72152 hom. )

Consequence

SERPINA9
NM_175739.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.581

Variant links:

Genes affected

SERPINA9 (HGNC:15995): (serpin family A member 9) Enables serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in cytoplasm and membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SERPINA9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00118348).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA9	NM_175739.4 link	c.653C>T	p.Pro218Leu	missense_variant	Exon 3 of 5	ENST00000674397.2	NP_783866.3	Q86WD7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA9	ENST00000674397.2 link	c.653C>T	p.Pro218Leu	missense_variant	Exon 3 of 5		NM_175739.4	ENSP00000501517.1		Q86WD7-1

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42785

AN:

152048

Hom.:

6440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.337

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.299

Gnomad EAS

AF:

0.433

Gnomad SAS

AF:

0.370

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.301

Gnomad OTH

AF:

0.296

GnomAD3 exomes

AF:

0.319

AC:

79139

AN:

248242

Hom.:

13106

AF XY:

0.320

AC XY:

43134

AN XY:

134596

show subpopulations

Gnomad AFR exome

AF:

0.163

Gnomad AMR exome

AF:

0.357

Gnomad ASJ exome

AF:

0.301

Gnomad EAS exome

AF:

0.440

Gnomad SAS exome

AF:

0.355

Gnomad FIN exome

AF:

0.319

Gnomad NFE exome

AF:

0.301

Gnomad OTH exome

AF:

0.316

GnomAD4 exome

AF:

0.312

AC:

455417

AN:

1458610

Hom.:

72152

Cov.:

AF XY:

0.314

AC XY:

227356

AN XY:

724890

show subpopulations

Gnomad4 AFR exome

AF:

0.163

Gnomad4 AMR exome

AF:

0.362

Gnomad4 ASJ exome

AF:

0.307

Gnomad4 EAS exome

AF:

0.452

Gnomad4 SAS exome

AF:

0.352

Gnomad4 FIN exome

AF:

0.323

Gnomad4 NFE exome

AF:

0.307

Gnomad4 OTH exome

AF:

0.314

GnomAD4 genome

AF:

0.281

AC:

42817

AN:

152166

Hom.:

6444

Cov.:

AF XY:

0.285

AC XY:

21230

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.174

Gnomad4 AMR

AF:

0.359

Gnomad4 ASJ

AF:

0.299

Gnomad4 EAS

AF:

0.433

Gnomad4 SAS

AF:

0.371

Gnomad4 FIN

AF:

0.339

Gnomad4 NFE

AF:

0.301

Gnomad4 OTH

AF:

0.303

Alfa

AF:

0.301

Hom.:

16552

Bravo

AF:

0.275

TwinsUK

AF:

0.307

AC:

1140

ALSPAC

AF:

0.319

AC:

1230

ESP6500AA

AF:

0.162

AC:

622

ESP6500EA

AF:

0.301

AC:

2486

ExAC

AF:

0.314

AC:

37964

Asia WGS

AF:

0.414

AC:

1440

AN:

3478

EpiCase

AF:

0.301

EpiControl

AF:

0.299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.16

.;.;.;.;T;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.69

T;T;T;T;T;T

MetaRNN

Benign

0.0012

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

.;.;.;.;M;.

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-6.2

D;D;D;D;D;D

REVEL

Benign

0.25

Sift

Uncertain

0.011

D;T;D;D;T;D

Sift4G

Benign

0.17

T;T;T;T;T;T

Polyphen

0.39

B;P;.;B;B;B

Vest4

0.18

MPC

0.019

ClinPred

0.034

GERP RS

1.9

Varity_R

0.19

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over