14-94463217-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_175739.4(SERPINA9):​c.1130G>C​(p.Arg377Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R377Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

SERPINA9
NM_175739.4 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.264
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SERPINA9NM_175739.4 linkc.1130G>C p.Arg377Pro missense_variant Exon 5 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.1130G>C p.Arg377Pro missense_variant Exon 5 of 5 NM_175739.4 ENSP00000501517.1 Q86WD7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461846
Hom.:
0
Cov.:
36
AF XY:
0.00
AC XY:
0
AN XY:
727224
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Benign
-0.016
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
15
DANN
Benign
0.89
DEOGEN2
Benign
0.17
.;.;.;.;T
Eigen
Benign
-0.75
Eigen_PC
Benign
-0.81
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.76
T;T;T;T;T
M_CAP
Uncertain
0.089
D
MetaRNN
Uncertain
0.58
D;D;D;D;D
MetaSVM
Benign
-0.45
T
MutationAssessor
Uncertain
2.2
.;.;.;.;M
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-1.9
N;D;D;N;N
REVEL
Benign
0.17
Sift
Benign
0.12
T;T;D;T;D
Sift4G
Benign
0.23
T;T;T;T;T
Polyphen
0.086
B;B;.;B;.
Vest4
0.50
MutPred
0.77
.;.;.;Gain of ubiquitination at K397 (P = 0.0317);.;
MVP
0.66
MPC
0.13
ClinPred
0.44
T
GERP RS
2.2
Varity_R
0.89
gMVP
0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-94929554; API