14-94467358-G-A

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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 0.28 ( 6444 hom., cov: 33)
Exomes 𝑓: 0.31 ( 72152 hom. )

Consequence

SERPINA9
NM_175739.4 missense

Scores

1
2
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.581

Publications

25 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]

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=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
SERPINA9NM_175739.4 linkc.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
SERPINA9ENST00000674397.2 linkc.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.:
33
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
GnomAD2 exomes
AF:
0.319
AC:
79139
AN:
248242
AF XY:
0.320
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 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.:
35
AF XY:
0.314
AC XY:
227356
AN XY:
724890
show subpopulations
African (AFR)
AF:
0.163
AC:
5447
AN:
33408
American (AMR)
AF:
0.362
AC:
16174
AN:
44618
Ashkenazi Jewish (ASJ)
AF:
0.307
AC:
8009
AN:
26110
East Asian (EAS)
AF:
0.452
AC:
17885
AN:
39608
South Asian (SAS)
AF:
0.352
AC:
30310
AN:
86082
European-Finnish (FIN)
AF:
0.323
AC:
17224
AN:
53346
Middle Eastern (MID)
AF:
0.232
AC:
1334
AN:
5758
European-Non Finnish (NFE)
AF:
0.307
AC:
340110
AN:
1109472
Other (OTH)
AF:
0.314
AC:
18924
AN:
60208
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.497
Heterozygous variant carriers
0
16699
33397
50096
66794
83493
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
11318
22636
33954
45272
56590
<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:
0.281
AC:
42817
AN:
152166
Hom.:
6444
Cov.:
33
AF XY:
0.285
AC XY:
21230
AN XY:
74378
show subpopulations
African (AFR)
AF:
0.174
AC:
7222
AN:
41530
American (AMR)
AF:
0.359
AC:
5490
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.299
AC:
1036
AN:
3470
East Asian (EAS)
AF:
0.433
AC:
2233
AN:
5154
South Asian (SAS)
AF:
0.371
AC:
1791
AN:
4826
European-Finnish (FIN)
AF:
0.339
AC:
3598
AN:
10598
Middle Eastern (MID)
AF:
0.218
AC:
64
AN:
294
European-Non Finnish (NFE)
AF:
0.301
AC:
20438
AN:
67990
Other (OTH)
AF:
0.303
AC:
639
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1611
3222
4833
6444
8055
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
432
864
1296
1728
2160
<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:
0.296
Hom.:
22130
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
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
11
DANN
Benign
0.93
DEOGEN2
Benign
0.16
.;.;.;.;T;.
Eigen
Benign
-0.61
Eigen_PC
Benign
-0.74
FATHMM_MKL
Benign
0.14
N
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
T
MutationAssessor
Uncertain
2.4
.;.;.;.;M;.
PhyloP100
0.58
PrimateAI
Benign
0.36
T
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
T
GERP RS
1.9
Varity_R
0.19
gMVP
0.31
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs17090921; hg19: chr14-94933695; COSMIC: COSV54073248; COSMIC: COSV54073248; API