Genetic Variant SERPINA10:p.Gln384Arg (chr14-94284149-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001100607.3(SERPINA10):c.1151A>G(p.Gln384Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,613,922 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q384Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0078 ( 10 hom., cov: 32)

Exomes 𝑓: 0.010 ( 95 hom. )

Consequence

SERPINA10
NM_001100607.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.37

Publications

15 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0077571273).

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100607.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA10	NM_001100607.3	MANE Select	c.1151A>G	p.Gln384Arg	missense	Exon 5 of 5	NP_001094077.1	Q9UK55
	SERPINA10	NM_016186.3		c.1151A>G	p.Gln384Arg	missense	Exon 5 of 5	NP_057270.1	Q9UK55

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINA10	ENST00000261994.9	TSL:1 MANE Select	c.1151A>G	p.Gln384Arg	missense	Exon 5 of 5	ENSP00000261994.4	Q9UK55
SERPINA10	ENST00000554723.5	TSL:1	c.1271A>G	p.Gln424Arg	missense	Exon 5 of 5	ENSP00000450896.1	G3V2W1
SERPINA10	ENST00000393096.5	TSL:1	c.1151A>G	p.Gln384Arg	missense	Exon 5 of 5	ENSP00000376809.1	Q9UK55

Frequencies

GnomAD3 genomes

AF:

0.00782

AC:

1190

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0230

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0116

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00806

AC:

2013

AN:

249768

AF XY:

0.00836

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00266

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0186

Gnomad NFE exome

AF:

0.0120

Gnomad OTH exome

AF:

0.00735

GnomAD4 exome

AF:

0.0102

AC:

14960

AN:

1461558

Hom.:

Cov.:

AF XY:

0.00995

AC XY:

7232

AN XY:

727104

show subpopulations

African (AFR)

AF:

0.00158

AC:

AN:

33476

American (AMR)

AF:

0.00293

AC:

131

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000727

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00348

AC:

300

AN:

86254

European-Finnish (FIN)

AF:

0.0191

AC:

1020

AN:

53382

Middle Eastern (MID)

AF:

0.0108

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0116

AC:

12943

AN:

1111742

Other (OTH)

AF:

0.00715

AC:

432

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

712

1423

2135

2846

3558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

480

960

1440

1920

2400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00781

AC:

1190

AN:

152364

Hom.:

Cov.:

AF XY:

0.00786

AC XY:

586

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.00180

AC:

AN:

41588

American (AMR)

AF:

0.00248

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00228

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0230

AC:

244

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0116

AC:

789

AN:

68028

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

119

178

238

297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0100

Hom.:

Bravo

AF:

0.00643

TwinsUK

AF:

0.0129

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0114

AC:

ExAC

AF:

0.00823

AC:

999

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0118

EpiControl

AF:

0.0103

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.44

Eigen

Benign

0.062

Eigen_PC

Benign

0.091

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0078

MetaSVM

Uncertain

0.34

MutationAssessor

Uncertain

2.2

PhyloP100

3.4

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.40

Sift

Benign

0.13

Sift4G

Uncertain

0.051

Polyphen

0.23

Vest4

0.29

MVP

0.64

MPC

0.062

ClinPred

0.020

GERP RS

5.2

Varity_R

0.88

gMVP

0.75

Mutation Taster

=85/15

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over