Genetic Variant NM_001100607.3:c.811G>A (chr14-94288467-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001100607.3(SERPINA10):c.811G>A(p.Gly271Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,614,006 control chromosomes in the GnomAD database, including 448 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.

Frequency

Genomes: 𝑓 0.031 ( 198 hom., cov: 32)

Exomes 𝑓: 0.0094 ( 250 hom. )

Consequence

SERPINA10
NM_001100607.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.439

Publications

10 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016829967).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA10	NM_001100607.3 link	c.811G>A	p.Gly271Ser	missense_variant	Exon 3 of 5	ENST00000261994.9	NP_001094077.1	Q9UK55A0A024R6I6
SERPINA10	NM_016186.3 link	c.811G>A	p.Gly271Ser	missense_variant	Exon 3 of 5		NP_057270.1	Q9UK55A0A024R6I6
SERPINA10	XM_017021353.2 link	c.931G>A	p.Gly311Ser	missense_variant	Exon 4 of 6		XP_016876842.1	G3V2W1
SERPINA10	XM_005267733.6 link	c.811G>A	p.Gly271Ser	missense_variant	Exon 3 of 5		XP_005267790.1	Q9UK55A0A024R6I6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SERPINA10	ENST00000261994.9 link	c.811G>A	p.Gly271Ser	missense_variant	Exon 3 of 5	1	NM_001100607.3	ENSP00000261994.4	Q9UK55
SERPINA10	ENST00000554723.5 link	c.931G>A	p.Gly311Ser	missense_variant	Exon 3 of 5	1		ENSP00000450896.1	G3V2W1
SERPINA10	ENST00000393096.5 link	c.811G>A	p.Gly271Ser	missense_variant	Exon 3 of 5	1		ENSP00000376809.1	Q9UK55
SERPINA10	ENST00000554173.1 link	c.811G>A	p.Gly271Ser	missense_variant	Exon 2 of 4	1		ENSP00000450971.1	Q9UK55

Frequencies

GnomAD3 genomes

AF:

0.0307

AC:

4665

AN:

152000

Hom.:

200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0898

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0161

Gnomad ASJ

AF:

0.0288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.00654

Gnomad OTH

AF:

0.0244

GnomAD2 exomes

AF:

0.0142

AC:

3577

AN:

251456

AF XY:

0.0131

show subpopulations

Gnomad AFR exome

AF:

0.0920

Gnomad AMR exome

AF:

0.0123

Gnomad ASJ exome

AF:

0.0259

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00692

Gnomad OTH exome

AF:

0.0164

GnomAD4 exome

AF:

0.00940

AC:

13735

AN:

1461888

Hom.:

250

Cov.:

AF XY:

0.00947

AC XY:

6890

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.0927

AC:

3102

AN:

33478

American (AMR)

AF:

0.0124

AC:

555

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0279

AC:

728

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.0162

AC:

1397

AN:

86258

European-Finnish (FIN)

AF:

0.00150

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0744

AC:

429

AN:

5768

European-Non Finnish (NFE)

AF:

0.00584

AC:

6497

AN:

1112010

Other (OTH)

AF:

0.0156

AC:

943

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

882

1763

2645

3526

4408

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

290

580

870

1160

1450

<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:

0.0307

AC:

4668

AN:

152118

Hom.:

198

Cov.:

AF XY:

0.0299

AC XY:

2223

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.0897

AC:

3720

AN:

41472

American (AMR)

AF:

0.0161

AC:

246

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0288

AC:

100

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.0144

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00654

AC:

445

AN:

67996

Other (OTH)

AF:

0.0242

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

207

414

622

829

1036

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0166

Hom.:

120

Bravo

AF:

0.0340

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.0865

AC:

381

ESP6500EA

AF:

0.00814

AC:

ExAC

AF:

0.0161

AC:

1954

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0110

EpiControl

AF:

0.00972

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.099

T;.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0078

LIST_S2

Benign

0.36

.;T;T;.

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.3

N;.;N;N

PhyloP100

0.44

PrimateAI

Benign

0.25

PROVEAN

Benign

1.3

N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.24

T;T;T;T

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.11

B;.;B;B

Vest4

0.018

MPC

0.028

ClinPred

0.0027

GERP RS

-2.3

Varity_R

0.20

gMVP

0.54

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over