14-94284144-T-C

Position:

chr14-94284144-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001100607.3(SERPINA10):c.1156A>G(p.Thr386Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,613,996 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

SERPINA10
NM_001100607.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.559

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018436342).

BP6

Variant 14-94284144-T-C is Benign according to our data. Variant chr14-94284144-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2274702.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SERPINA10	NM_001100607.3 linkuse as main transcript	c.1156A>G	p.Thr386Ala	missense_variant	5/5	ENST00000261994.9
SERPINA10	NM_016186.3 linkuse as main transcript	c.1156A>G	p.Thr386Ala	missense_variant	5/5
SERPINA10	XM_017021353.2 linkuse as main transcript	c.1276A>G	p.Thr426Ala	missense_variant	6/6
SERPINA10	XM_005267733.6 linkuse as main transcript	c.1156A>G	p.Thr386Ala	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SERPINA10	ENST00000261994.9 linkuse as main transcript	c.1156A>G	p.Thr386Ala	missense_variant	5/5	1	NM_001100607.3	A2
SERPINA10	ENST00000554723.5 linkuse as main transcript	c.1276A>G	p.Thr426Ala	missense_variant	5/5	1		P4
SERPINA10	ENST00000393096.5 linkuse as main transcript	c.1156A>G	p.Thr386Ala	missense_variant	5/5	1		A2
SERPINA10	ENST00000554173.1 linkuse as main transcript	c.1156A>G	p.Thr386Ala	missense_variant	4/4	1		A2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000320

AC:

AN:

250022

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135248

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461754

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.000191

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:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.9

DANN

Benign

0.77

DEOGEN2

Benign

0.12

T;.;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.47

.;T;T;.

M_CAP

Benign

0.018

MetaRNN

Benign

0.018

T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

-1.8

N;.;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

3.1

N;N;N;N

REVEL

Benign

0.15

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.037

MVP

0.061

MPC

0.025

ClinPred

0.061

GERP RS

-3.1

Varity_R

0.19

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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