chr14-94290332-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001100607.3(SERPINA10):c.262C>T(p.Arg88*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00645 in 1,614,230 control chromosomes in the GnomAD database, including 84 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0053 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0066 ( 78 hom. )

Consequence

SERPINA10
NM_001100607.3 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.99

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 -16 ACMG points.

BP6

Variant 14-94290332-G-A is Benign according to our data. Variant chr14-94290332-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 979156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA10	NM_001100607.3 link	c.262C>T	p.Arg88*	stop_gained	Exon 2 of 5	ENST00000261994.9	NP_001094077.1	Q9UK55A0A024R6I6
SERPINA10	NM_016186.3 link	c.262C>T	p.Arg88*	stop_gained	Exon 2 of 5		NP_057270.1	Q9UK55A0A024R6I6
SERPINA10	XM_017021353.2 link	c.382C>T	p.Arg128*	stop_gained	Exon 3 of 6		XP_016876842.1	G3V2W1
SERPINA10	XM_005267733.6 link	c.262C>T	p.Arg88*	stop_gained	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.262C>T	p.Arg88*	stop_gained	Exon 2 of 5	1	NM_001100607.3	ENSP00000261994.4	Q9UK55
SERPINA10	ENST00000554723.5 link	c.382C>T	p.Arg128*	stop_gained	Exon 2 of 5	1		ENSP00000450896.1	G3V2W1
SERPINA10	ENST00000393096.5 link	c.262C>T	p.Arg88*	stop_gained	Exon 2 of 5	1		ENSP00000376809.1	Q9UK55
SERPINA10	ENST00000554173.1 link	c.262C>T	p.Arg88*	stop_gained	Exon 1 of 4	1		ENSP00000450971.1	Q9UK55

Frequencies

GnomAD3 genomes

AF:

0.00532

AC:

810

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00765

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.00630

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00718

AC:

1802

AN:

251086

AF XY:

0.00797

show subpopulations

Gnomad AFR exome

AF:

0.00234

Gnomad AMR exome

AF:

0.00726

Gnomad ASJ exome

AF:

0.0184

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00665

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.00657

AC:

9604

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00702

AC XY:

5105

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00272

AC:

AN:

33480

Gnomad4 AMR exome

AF:

0.00686

AC:

307

AN:

44724

Gnomad4 ASJ exome

AF:

0.0196

AC:

512

AN:

26136

Gnomad4 EAS exome

AF:

0.000151

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.0160

AC:

1382

AN:

86256

Gnomad4 FIN exome

AF:

0.00150

AC:

AN:

53418

Gnomad4 NFE exome

AF:

0.00565

AC:

6281

AN:

1112006

Gnomad4 Remaining exome

AF:

0.00901

AC:

544

AN:

60396

Heterozygous variant carriers

678

1356

2033

2711

3389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

230

460

690

920

1150

<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:

0.00530

AC:

808

AN:

152346

Hom.:

Cov.:

AF XY:

0.00554

AC XY:

413

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00164

AC:

0.00163501

AN:

0.00163501

Gnomad4 AMR

AF:

0.00764

AC:

0.00764406

AN:

0.00764406

Gnomad4 ASJ

AF:

0.0202

AC:

0.0201962

AN:

0.0201962

Gnomad4 EAS

AF:

0.000193

AC:

0.000193424

AN:

0.000193424

Gnomad4 SAS

AF:

0.0139

AC:

0.0138774

AN:

0.0138774

Gnomad4 FIN

AF:

0.00113

AC:

0.00112931

AN:

0.00112931

Gnomad4 NFE

AF:

0.00631

AC:

0.0063053

AN:

0.0063053

Gnomad4 OTH

AF:

0.0104

AC:

0.010397

AN:

0.010397

Heterozygous variant carriers

136

181

226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<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:

0.00715

Hom.:

Bravo

AF:

0.00521

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00756

AC:

ExAC

AF:

0.00749

AC:

909

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.0109

EpiControl

AF:

0.00942

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

LAMB2-related infantile-onset nephrotic syndrome

Benign:1

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:research

The heterozygous p.Arg88Ter variant in SERPINA10 has been identified in 3 individuals with venous thromboembolic disease, including an individual with Factor V Leiden, and 1 homozygous individual with autism spectrum disorder (PMID: 15461625, 22039093, 23352160), and has been identified in >1% of South Asian chromosomes and 6 homozygotes by ExAC (http://gnomad.broadinstitute.org/). A meta-analysis suggests this variant does not cause increased risk of disease (PMID: 18710385). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely benign for autosomal dominant venous thromboembolic disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.45

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.32

Eigen_PC

Benign

0.088

FATHMM_MKL

Uncertain

0.77

Vest4

0.85

GERP RS

3.0

Mutation Taster

=162/38

disease causing (fs/PTC)

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over