chr14-94289954-G-A

Variant summary

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

The NM_001100607.3(SERPINA10):​c.640C>T​(p.Arg214Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R214Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

SERPINA10
NM_001100607.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.278
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]

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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=0.13699192).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SERPINA10NM_001100607.3 linkuse as main transcriptc.640C>T p.Arg214Trp missense_variant 2/5 ENST00000261994.9
SERPINA10NM_016186.3 linkuse as main transcriptc.640C>T p.Arg214Trp missense_variant 2/5
SERPINA10XM_017021353.2 linkuse as main transcriptc.760C>T p.Arg254Trp missense_variant 3/6
SERPINA10XM_005267733.6 linkuse as main transcriptc.640C>T p.Arg214Trp missense_variant 2/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SERPINA10ENST00000261994.9 linkuse as main transcriptc.640C>T p.Arg214Trp missense_variant 2/51 NM_001100607.3 A2
SERPINA10ENST00000554723.5 linkuse as main transcriptc.760C>T p.Arg254Trp missense_variant 2/51 P4
SERPINA10ENST00000393096.5 linkuse as main transcriptc.640C>T p.Arg214Trp missense_variant 2/51 A2
SERPINA10ENST00000554173.1 linkuse as main transcriptc.640C>T p.Arg214Trp missense_variant 1/41 A2

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152180
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000915
AC:
23
AN:
251386
Hom.:
0
AF XY:
0.0000957
AC XY:
13
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000114
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000636
AC:
93
AN:
1461858
Hom.:
0
Cov.:
33
AF XY:
0.0000605
AC XY:
44
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000630
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152180
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000112
Hom.:
0
Bravo
AF:
0.0000529
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000576
AC:
7
EpiCase
AF:
0.000164
EpiControl
AF:
0.000178

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 GeneticsOct 03, 2022The c.640C>T (p.R214W) alteration is located in exon 2 (coding exon 1) of the SERPINA10 gene. This alteration results from a C to T substitution at nucleotide position 640, causing the arginine (R) at amino acid position 214 to be replaced by a tryptophan (W). 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
0.10
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
14
DANN
Benign
0.91
DEOGEN2
Uncertain
0.65
D;.;D;D
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.030
N
LIST_S2
Benign
0.36
.;T;T;.
M_CAP
Benign
0.065
D
MetaRNN
Benign
0.14
T;T;T;T
MetaSVM
Benign
-0.71
T
MutationAssessor
Benign
1.0
L;.;L;L
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.20
T
PROVEAN
Uncertain
-3.0
D;D;D;D
REVEL
Benign
0.20
Sift
Benign
0.075
T;D;T;T
Sift4G
Benign
0.062
T;T;T;T
Polyphen
0.010
B;.;B;B
Vest4
0.20
MutPred
0.52
Loss of disorder (P = 0.0137);.;Loss of disorder (P = 0.0137);Loss of disorder (P = 0.0137);
MVP
0.20
MPC
0.026
ClinPred
0.028
T
GERP RS
-6.2
Varity_R
0.13
gMVP
0.35

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs570402881; hg19: chr14-94756291; COSMIC: COSV100003982; API