Variant 14-94290457-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001100607.3(SERPINA10):c.137A>G(p.Lys46Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,612,922 control chromosomes in the GnomAD database, including 165,640 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.54 ( 25131 hom., cov: 32)

Exomes 𝑓: 0.43 ( 140509 hom. )

Consequence

SERPINA10
NM_001100607.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.48

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0357013E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SERPINA10	NM_001100607.3 linkuse as main transcript	c.137A>G	p.Lys46Arg	missense_variant	2/5	ENST00000261994.9	NP_001094077.1
SERPINA10	NM_016186.3 linkuse as main transcript	c.137A>G	p.Lys46Arg	missense_variant	2/5		NP_057270.1
SERPINA10	XM_017021353.2 linkuse as main transcript	c.257A>G	p.Lys86Arg	missense_variant	3/6		XP_016876842.1
SERPINA10	XM_005267733.6 linkuse as main transcript	c.137A>G	p.Lys46Arg	missense_variant	2/5		XP_005267790.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SERPINA10	ENST00000261994.9 linkuse as main transcript	c.137A>G	p.Lys46Arg	missense_variant	2/5	1	NM_001100607.3	ENSP00000261994	A2
SERPINA10	ENST00000554723.5 linkuse as main transcript	c.257A>G	p.Lys86Arg	missense_variant	2/5	1		ENSP00000450896	P4
SERPINA10	ENST00000393096.5 linkuse as main transcript	c.137A>G	p.Lys46Arg	missense_variant	2/5	1		ENSP00000376809	A2
SERPINA10	ENST00000554173.1 linkuse as main transcript	c.137A>G	p.Lys46Arg	missense_variant	1/4	1		ENSP00000450971	A2

Frequencies

GnomAD3 genomes

AF:

0.544

AC:

82628

AN:

151966

Hom.:

25067

Cov.:

show subpopulations

Gnomad AFR

AF:

0.822

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.492

Gnomad ASJ

AF:

0.564

Gnomad EAS

AF:

0.647

Gnomad SAS

AF:

0.615

Gnomad FIN

AF:

0.445

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.389

Gnomad OTH

AF:

0.539

GnomAD3 exomes

AF:

0.489

AC:

121166

AN:

247610

Hom.:

31796

AF XY:

0.488

AC XY:

65294

AN XY:

133874

show subpopulations

Gnomad AFR exome

AF:

0.829

Gnomad AMR exome

AF:

0.467

Gnomad ASJ exome

AF:

0.552

Gnomad EAS exome

AF:

0.649

Gnomad SAS exome

AF:

0.614

Gnomad FIN exome

AF:

0.434

Gnomad NFE exome

AF:

0.392

Gnomad OTH exome

AF:

0.482

GnomAD4 exome

AF:

0.427

AC:

623399

AN:

1460838

Hom.:

140509

Cov.:

AF XY:

0.431

AC XY:

313357

AN XY:

726626

show subpopulations

Gnomad4 AFR exome

AF:

0.844

Gnomad4 AMR exome

AF:

0.474

Gnomad4 ASJ exome

AF:

0.554

Gnomad4 EAS exome

AF:

0.645

Gnomad4 SAS exome

AF:

0.615

Gnomad4 FIN exome

AF:

0.429

Gnomad4 NFE exome

AF:

0.383

Gnomad4 OTH exome

AF:

0.474

GnomAD4 genome

AF:

0.544

AC:

82746

AN:

152084

Hom.:

25131

Cov.:

AF XY:

0.548

AC XY:

40742

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.822

Gnomad4 AMR

AF:

0.493

Gnomad4 ASJ

AF:

0.564

Gnomad4 EAS

AF:

0.648

Gnomad4 SAS

AF:

0.616

Gnomad4 FIN

AF:

0.445

Gnomad4 NFE

AF:

0.389

Gnomad4 OTH

AF:

0.535

Alfa

AF:

0.435

Hom.:

29802

Bravo

AF:

0.558

TwinsUK

AF:

0.371

AC:

1377

ALSPAC

AF:

0.381

AC:

1468

ESP6500AA

AF:

0.808

AC:

3559

ESP6500EA

AF:

0.393

AC:

3376

ExAC

AF:

0.488

AC:

59292

Asia WGS

AF:

0.593

AC:

2064

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.013

DANN

Benign

0.74

DEOGEN2

Benign

0.040

T;.;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.25

.;T;T;.

MetaRNN

Benign

0.0000010

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.69

N;.;N;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.20

PROVEAN

Benign

0.0

N;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.82

T;T;T;T

Sift4G

Benign

0.78

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.026

MPC

0.023

ClinPred

0.0021

GERP RS

-0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.015

gMVP

0.22

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