Variant chr14-94288306-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000261994.9(SERPINA10):c.972G>A(p.Trp324Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 1,613,964 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0040 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 17 hom. )

Consequence

SERPINA10
ENST00000261994.9 stop_gained

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 2.67

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 Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SERPINA10	NM_001100607.3 linkuse as main transcript	c.972G>A	p.Trp324Ter	stop_gained	3/5	ENST00000261994.9	NP_001094077.1
SERPINA10	NM_016186.3 linkuse as main transcript	c.972G>A	p.Trp324Ter	stop_gained	3/5		NP_057270.1
SERPINA10	XM_017021353.2 linkuse as main transcript	c.1092G>A	p.Trp364Ter	stop_gained	4/6		XP_016876842.1
SERPINA10	XM_005267733.6 linkuse as main transcript	c.972G>A	p.Trp324Ter	stop_gained	3/5		XP_005267790.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SERPINA10	ENST00000261994.9 linkuse as main transcript	c.972G>A	p.Trp324Ter	stop_gained	3/5	1	NM_001100607.3	ENSP00000261994	A2
SERPINA10	ENST00000554723.5 linkuse as main transcript	c.1092G>A	p.Trp364Ter	stop_gained	3/5	1		ENSP00000450896	P4
SERPINA10	ENST00000393096.5 linkuse as main transcript	c.972G>A	p.Trp324Ter	stop_gained	3/5	1		ENSP00000376809	A2
SERPINA10	ENST00000554173.1 linkuse as main transcript	c.972G>A	p.Trp324Ter	stop_gained	2/4	1		ENSP00000450971	A2

Frequencies

GnomAD3 genomes

AF:

0.00403

AC:

613

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.0158

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00545

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00416

AC:

1046

AN:

251466

Hom.:

AF XY:

0.00414

AC XY:

562

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00163

Gnomad FIN exome

AF:

0.0164

Gnomad NFE exome

AF:

0.00498

Gnomad OTH exome

AF:

0.00472

GnomAD4 exome

AF:

0.00435

AC:

6352

AN:

1461692

Hom.:

Cov.:

AF XY:

0.00431

AC XY:

3137

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00190

Gnomad4 FIN exome

AF:

0.0171

Gnomad4 NFE exome

AF:

0.00448

Gnomad4 OTH exome

AF:

0.00345

GnomAD4 genome

AF:

0.00403

AC:

613

AN:

152272

Hom.:

Cov.:

AF XY:

0.00414

AC XY:

308

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000891

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.0158

Gnomad4 NFE

AF:

0.00545

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00456

Hom.:

Bravo

AF:

0.00242

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00581

AC:

ExAC

AF:

0.00424

AC:

515

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00480

EpiControl

AF:

0.00504

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Venous thrombosis, susceptibility to

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Oct 01, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.62

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.96

MutationTaster

Benign

1.0

A;A;A;A

Vest4

0.96

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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