Variant 14-94290413-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001100607.3(SERPINA10):c.181A>C(p.Ser61Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,613,892 control chromosomes in the GnomAD database, including 1 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S61G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

SERPINA10
NM_001100607.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.21

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]

SERPINA10 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0052494407).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SERPINA10	NM_001100607.3 linkuse as main transcript	c.181A>C	p.Ser61Arg	missense_variant	2/5	ENST00000261994.9
SERPINA10	NM_016186.3 linkuse as main transcript	c.181A>C	p.Ser61Arg	missense_variant	2/5
SERPINA10	XM_017021353.2 linkuse as main transcript	c.301A>C	p.Ser101Arg	missense_variant	3/6
SERPINA10	XM_005267733.6 linkuse as main transcript	c.181A>C	p.Ser61Arg	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SERPINA10	ENST00000261994.9 linkuse as main transcript	c.181A>C	p.Ser61Arg	missense_variant	2/5	1	NM_001100607.3	A2
SERPINA10	ENST00000554723.5 linkuse as main transcript	c.301A>C	p.Ser101Arg	missense_variant	2/5	1		P4
SERPINA10	ENST00000393096.5 linkuse as main transcript	c.181A>C	p.Ser61Arg	missense_variant	2/5	1		A2
SERPINA10	ENST00000554173.1 linkuse as main transcript	c.181A>C	p.Ser61Arg	missense_variant	1/4	1		A2

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152060

Hom.:

Cov.:

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:

0.00213

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000172

AC:

AN:

249708

Hom.:

AF XY:

0.000185

AC XY:

AN XY:

135030

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00218

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000135

AC:

198

AN:

1461714

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

101

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00486

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00214

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00000275

Hom.:

7433

ExAC

AF:

0.000173

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.0040

DANN

Benign

0.13

DEOGEN2

Benign

0.045

T;.;T;T

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.34

.;T;T;.

M_CAP

Benign

0.0024

MetaRNN

Benign

0.0052

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

N;.;N;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.38

N;N;N;N

REVEL

Benign

0.25

Sift

Benign

0.53

T;T;T;T

Sift4G

Benign

0.34

T;T;T;T

Polyphen

0.22

B;.;B;B

Vest4

0.17

MutPred

0.19

Loss of phosphorylation at S61 (P = 0.0022);.;Loss of phosphorylation at S61 (P = 0.0022);Loss of phosphorylation at S61 (P = 0.0022);

MVP

0.16

MPC

0.027

ClinPred

0.013

GERP RS

-2.3

Varity_R

0.092

gMVP

0.37

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over