Genetic Variant SERPINA10:p.Ser61Gly (chr14-94290413-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001100607.3(SERPINA10):c.181A>G(p.Ser61Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,613,816 control chromosomes in the GnomAD database, including 37,756 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.25 ( 6045 hom., cov: 33)

Exomes 𝑓: 0.19 ( 31711 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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.489452E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA10	NM_001100607.3 link	c.181A>G	p.Ser61Gly	missense_variant	Exon 2 of 5	ENST00000261994.9	NP_001094077.1	Q9UK55A0A024R6I6
SERPINA10	NM_016186.3 link	c.181A>G	p.Ser61Gly	missense_variant	Exon 2 of 5		NP_057270.1	Q9UK55A0A024R6I6
SERPINA10	XM_017021353.2 link	c.301A>G	p.Ser101Gly	missense_variant	Exon 3 of 6		XP_016876842.1	G3V2W1
SERPINA10	XM_005267733.6 link	c.181A>G	p.Ser61Gly	missense_variant	Exon 2 of 5		XP_005267790.1	Q9UK55A0A024R6I6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SERPINA10	ENST00000261994.9 link	c.181A>G	p.Ser61Gly	missense_variant	Exon 2 of 5	1	NM_001100607.3	ENSP00000261994.4	Q9UK55
SERPINA10	ENST00000554723.5 link	c.301A>G	p.Ser101Gly	missense_variant	Exon 2 of 5	1		ENSP00000450896.1	G3V2W1
SERPINA10	ENST00000393096.5 link	c.181A>G	p.Ser61Gly	missense_variant	Exon 2 of 5	1		ENSP00000376809.1	Q9UK55
SERPINA10	ENST00000554173.1 link	c.181A>G	p.Ser61Gly	missense_variant	Exon 1 of 4	1		ENSP00000450971.1	Q9UK55

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38297

AN:

152032

Hom.:

6025

Cov.:

show subpopulations

Gnomad AFR

AF:

0.404

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.177

Gnomad EAS

AF:

0.589

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.206

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.234

GnomAD3 exomes

AF:

0.227

AC:

56806

AN:

249708

Hom.:

8376

AF XY:

0.223

AC XY:

30178

AN XY:

135030

show subpopulations

Gnomad AFR exome

AF:

0.412

Gnomad AMR exome

AF:

0.169

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.587

Gnomad SAS exome

AF:

0.258

Gnomad FIN exome

AF:

0.192

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.198

GnomAD4 exome

AF:

0.191

AC:

278937

AN:

1461666

Hom.:

31711

Cov.:

AF XY:

0.192

AC XY:

139375

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.422

Gnomad4 AMR exome

AF:

0.171

Gnomad4 ASJ exome

AF:

0.173

Gnomad4 EAS exome

AF:

0.587

Gnomad4 SAS exome

AF:

0.255

Gnomad4 FIN exome

AF:

0.188

Gnomad4 NFE exome

AF:

0.164

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.252

AC:

38368

AN:

152150

Hom.:

6045

Cov.:

AF XY:

0.254

AC XY:

18900

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.405

Gnomad4 AMR

AF:

0.170

Gnomad4 ASJ

AF:

0.177

Gnomad4 EAS

AF:

0.589

Gnomad4 SAS

AF:

0.254

Gnomad4 FIN

AF:

0.206

Gnomad4 NFE

AF:

0.164

Gnomad4 OTH

AF:

0.233

Alfa

AF:

0.183

Hom.:

7433

Bravo

AF:

0.259

TwinsUK

AF:

0.156

AC:

579

ALSPAC

AF:

0.167

AC:

645

ESP6500AA

AF:

0.397

AC:

1748

ESP6500EA

AF:

0.164

AC:

1414

ExAC

AF:

0.231

AC:

28016

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.0060

DANN

Benign

0.15

DEOGEN2

Benign

0.045

T;.;T;T

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0041

LIST_S2

Benign

0.27

.;T;T;.

MetaRNN

Benign

0.000015

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.34

N;.;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.27

N;N;N;N

REVEL

Benign

0.24

Sift

Benign

0.43

T;T;T;T

Sift4G

Benign

0.32

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.054

MPC

0.024

ClinPred

0.00083

GERP RS

-2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.082

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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