Variant chr14-94290074-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001100607.3(SERPINA10):c.520G>A(p.Val174Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,614,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

SERPINA10
NM_001100607.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.286

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.007145107).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SERPINA10	NM_001100607.3 linkuse as main transcript	c.520G>A	p.Val174Ile	missense_variant	2/5	ENST00000261994.9
SERPINA10	NM_016186.3 linkuse as main transcript	c.520G>A	p.Val174Ile	missense_variant	2/5
SERPINA10	XM_017021353.2 linkuse as main transcript	c.640G>A	p.Val214Ile	missense_variant	3/6
SERPINA10	XM_005267733.6 linkuse as main transcript	c.520G>A	p.Val174Ile	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SERPINA10	ENST00000261994.9 linkuse as main transcript	c.520G>A	p.Val174Ile	missense_variant	2/5	1	NM_001100607.3	A2
SERPINA10	ENST00000554723.5 linkuse as main transcript	c.640G>A	p.Val214Ile	missense_variant	2/5	1		P4
SERPINA10	ENST00000393096.5 linkuse as main transcript	c.520G>A	p.Val174Ile	missense_variant	2/5	1		A2
SERPINA10	ENST00000554173.1 linkuse as main transcript	c.520G>A	p.Val174Ile	missense_variant	1/4	1		A2

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

251430

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000609

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00194

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000519

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000168

Hom.:

Bravo

AF:

0.000555

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000123

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

The c.520G>A (p.V174I) alteration is located in exon 2 (coding exon 1) of the SERPINA10 gene. This alteration results from a G to A substitution at nucleotide position 520, causing the valine (V) at amino acid position 174 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Benign

1.4

DANN

Benign

0.60

DEOGEN2

Benign

0.093

T;.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.035

M_CAP

Benign

0.033

MetaRNN

Benign

0.0071

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.14

N;.;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

0.30

N;N;N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0040

B;.;B;B

Vest4

0.088

MVP

0.095

MPC

0.024

ClinPred

0.0063

GERP RS

0.97

Varity_R

0.11

gMVP

0.13

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