dbSNP rs11628722: SERPINA9:p.Val330Ala (chr14-94464768-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_175739.4(SERPINA9):c.989T>C(p.Val330Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,612,534 control chromosomes in the GnomAD database, including 533,131 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.71 ( 40562 hom., cov: 32)

Exomes 𝑓: 0.82 ( 492569 hom. )

Consequence

SERPINA9
NM_175739.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.900

Publications

33 publications found

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:

ENSG00000256357 (HGNC:):

ENSG00000256357 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.8559922E-6).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA9	NM_175739.4 link	c.989T>C	p.Val330Ala	missense_variant	Exon 4 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.989T>C	p.Val330Ala	missense_variant	Exon 4 of 5		NM_175739.4	ENSP00000501517.1		Q86WD7-1

Frequencies

GnomAD3 genomes

AF:

0.710

AC:

107912

AN:

151966

Hom.:

40552

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.936

Gnomad AMR

AF:

0.744

Gnomad ASJ

AF:

0.757

Gnomad EAS

AF:

0.614

Gnomad SAS

AF:

0.857

Gnomad FIN

AF:

0.855

Gnomad MID

AF:

0.772

Gnomad NFE

AF:

0.831

Gnomad OTH

AF:

0.742

GnomAD2 exomes

AF:

0.776

AC:

193539

AN:

249310

AF XY:

0.790

show subpopulations

Gnomad AFR exome

AF:

0.433

Gnomad AMR exome

AF:

0.693

Gnomad ASJ exome

AF:

0.758

Gnomad EAS exome

AF:

0.625

Gnomad FIN exome

AF:

0.852

Gnomad NFE exome

AF:

0.836

Gnomad OTH exome

AF:

0.795

GnomAD4 exome

AF:

0.818

AC:

1194100

AN:

1460450

Hom.:

492569

Cov.:

AF XY:

0.820

AC XY:

596127

AN XY:

726634

show subpopulations

African (AFR)

AF:

0.428

AC:

14325

AN:

33452

American (AMR)

AF:

0.702

AC:

31352

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.761

AC:

19869

AN:

26124

East Asian (EAS)

AF:

0.619

AC:

24548

AN:

39670

South Asian (SAS)

AF:

0.859

AC:

74011

AN:

86200

European-Finnish (FIN)

AF:

0.855

AC:

45659

AN:

53416

Middle Eastern (MID)

AF:

0.779

AC:

4493

AN:

5764

European-Non Finnish (NFE)

AF:

0.839

AC:

932056

AN:

1110820

Other (OTH)

AF:

0.792

AC:

47787

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

10240

20480

30721

40961

51201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20970

41940

62910

83880

104850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.710

AC:

107967

AN:

152084

Hom.:

40562

Cov.:

AF XY:

0.712

AC XY:

52904

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.446

AC:

18474

AN:

41440

American (AMR)

AF:

0.744

AC:

11367

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.757

AC:

2626

AN:

3470

East Asian (EAS)

AF:

0.614

AC:

3173

AN:

5166

South Asian (SAS)

AF:

0.857

AC:

4130

AN:

4820

European-Finnish (FIN)

AF:

0.855

AC:

9058

AN:

10590

Middle Eastern (MID)

AF:

0.762

AC:

224

AN:

294

European-Non Finnish (NFE)

AF:

0.831

AC:

56485

AN:

68000

Other (OTH)

AF:

0.746

AC:

1576

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1382

2764

4145

5527

6909

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

814

1628

2442

3256

4070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.784

Hom.:

162795

Bravo

AF:

0.687

ESP6500AA

AF:

0.464

AC:

1705

ESP6500EA

AF:

0.834

AC:

6820

ExAC

AF:

0.777

AC:

93866

Asia WGS

AF:

0.737

AC:

2563

AN:

3478

EpiCase

AF:

0.824

EpiControl

AF:

0.825

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Benign

4.0

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.026

.;.;.;.;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0052

LIST_S2

Benign

0.16

T;T;T;T;T;T

MetaRNN

Benign

0.0000019

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.73

.;.;.;.;N;.

PhyloP100

0.90

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.29

N;N;N;N;N;N

REVEL

Benign

0.27

Sift

Benign

1.0

T;T;T;T;T;T

Sift4G

Benign

0.42

T;T;T;T;T;T

Polyphen

0.0

B;B;.;B;B;B

Vest4

0.025

MPC

0.016

ClinPred

0.00075

GERP RS

2.1

Varity_R

0.027

gMVP

0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over