rs2232698

Positions:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001100607.3(SERPINA10):c.262C>T(p.Arg88Ter) 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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE
SERPINA10	NM_001100607.3 linkuse as main transcript	c.262C>T	p.Arg88Ter	stop_gained	2/5	ENST00000261994.9
SERPINA10	NM_016186.3 linkuse as main transcript	c.262C>T	p.Arg88Ter	stop_gained	2/5
SERPINA10	XM_017021353.2 linkuse as main transcript	c.382C>T	p.Arg128Ter	stop_gained	3/6
SERPINA10	XM_005267733.6 linkuse as main transcript	c.262C>T	p.Arg88Ter	stop_gained	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SERPINA10	ENST00000261994.9 linkuse as main transcript	c.262C>T	p.Arg88Ter	stop_gained	2/5	1	NM_001100607.3	A2
SERPINA10	ENST00000554723.5 linkuse as main transcript	c.382C>T	p.Arg128Ter	stop_gained	2/5	1		P4
SERPINA10	ENST00000393096.5 linkuse as main transcript	c.262C>T	p.Arg88Ter	stop_gained	2/5	1		A2
SERPINA10	ENST00000554173.1 linkuse as main transcript	c.262C>T	p.Arg88Ter	stop_gained	1/4	1		A2

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

GnomAD3 exomes

AF:

0.00718

AC:

1802

AN:

251086

Hom.:

AF XY:

0.00797

AC XY:

1081

AN XY:

135716

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 SAS exome

AF:

0.0156

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

Gnomad4 AMR exome

AF:

0.00686

Gnomad4 ASJ exome

AF:

0.0196

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0160

Gnomad4 FIN exome

AF:

0.00150

Gnomad4 NFE exome

AF:

0.00565

Gnomad4 OTH exome

AF:

0.00901

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

Gnomad4 AMR

AF:

0.00764

Gnomad4 ASJ

AF:

0.0202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00631

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00744

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

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

LAMB2-related infantile-onset nephrotic syndrome

Benign:1

Likely benign, criteria provided, single submitter

research

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

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

MutationTaster

Benign

1.0

A;A;A;A

Vest4

0.85

GERP RS

3.0

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