chr14-94284138-T-C

Variant summary

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

The NM_001100607.3(SERPINA10):ā€‹c.1162A>Gā€‹(p.Ile388Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

SERPINA10
NM_001100607.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.23
Variant links:
Genes affected
SERPINA10 (HGNC:15996): (serpin family A member 10) The protein encoded by this gene belongs to the serpin family. It is predominantly expressed in the liver and secreted in plasma. It inhibits the activity of coagulation factors Xa and XIa in the presence of protein Z, calcium and phospholipid. Mutations in this gene are associated with venous thrombosis. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, May 2010]

Genome browser will be placed here

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=0.18145895).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SERPINA10NM_001100607.3 linkuse as main transcriptc.1162A>G p.Ile388Val missense_variant 5/5 ENST00000261994.9
SERPINA10NM_016186.3 linkuse as main transcriptc.1162A>G p.Ile388Val missense_variant 5/5
SERPINA10XM_017021353.2 linkuse as main transcriptc.1282A>G p.Ile428Val missense_variant 6/6
SERPINA10XM_005267733.6 linkuse as main transcriptc.1162A>G p.Ile388Val missense_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SERPINA10ENST00000261994.9 linkuse as main transcriptc.1162A>G p.Ile388Val missense_variant 5/51 NM_001100607.3 A2
SERPINA10ENST00000554723.5 linkuse as main transcriptc.1282A>G p.Ile428Val missense_variant 5/51 P4
SERPINA10ENST00000393096.5 linkuse as main transcriptc.1162A>G p.Ile388Val missense_variant 5/51 A2
SERPINA10ENST00000554173.1 linkuse as main transcriptc.1162A>G p.Ile388Val missense_variant 4/41 A2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152244
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
250170
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135324
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.00000889
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461800
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727220
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152244
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsDec 17, 2023The c.1162A>G (p.I388V) alteration is located in exon 5 (coding exon 4) of the SERPINA10 gene. This alteration results from a A to G substitution at nucleotide position 1162, causing the isoleucine (I) at amino acid position 388 to be replaced by a valine (V). 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
0.088
BayesDel_addAF
Benign
-0.093
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
15
DANN
Benign
0.91
DEOGEN2
Benign
0.17
T;.;T;T
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.47
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.68
.;T;T;.
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.18
T;T;T;T
MetaSVM
Benign
-0.56
T
MutationAssessor
Benign
0.72
N;.;N;N
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.83
N;N;N;N
REVEL
Benign
0.14
Sift
Benign
0.15
T;T;T;T
Sift4G
Benign
0.34
T;T;T;T
Polyphen
0.037
B;.;B;B
Vest4
0.087
MutPred
0.75
Gain of disorder (P = 0.0935);.;Gain of disorder (P = 0.0935);Gain of disorder (P = 0.0935);
MVP
0.19
MPC
0.029
ClinPred
0.087
T
GERP RS
2.0
Varity_R
0.32
gMVP
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs773811944; hg19: chr14-94750475; API