Variant 14-94469470-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_175739.4(SERPINA9):c.371C>T(p.Pro124Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,614,148 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0082 ( 7 hom., cov: 32)

Exomes 𝑓: 0.011 ( 108 hom. )

Consequence

SERPINA9
NM_175739.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.518

Variant links:

Genes affected

SERPINA9 (HGNC:15995): (serpin family A member 9) Enables serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in cytoplasm and membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SERPINA9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005036205).

BP6

Variant 14-94469470-G-A is Benign according to our data. Variant chr14-94469470-G-A is described in ClinVar as [Benign]. Clinvar id is 2644479.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINA9	NM_175739.4 linkuse as main transcript	c.371C>T	p.Pro124Leu	missense_variant	2/5	ENST00000674397.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINA9	ENST00000674397.2 linkuse as main transcript	c.371C>T	p.Pro124Leu	missense_variant	2/5		NM_175739.4	P2	Q86WD7-1

Frequencies

GnomAD3 genomes

AF:

0.00818

AC:

1244

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0169

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.00836

AC:

2085

AN:

249538

Hom.:

AF XY:

0.00819

AC XY:

1109

AN XY:

135380

show subpopulations

Gnomad AFR exome

AF:

0.00161

Gnomad AMR exome

AF:

0.00513

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.0162

Gnomad NFE exome

AF:

0.0127

Gnomad OTH exome

AF:

0.00841

GnomAD4 exome

AF:

0.0111

AC:

16253

AN:

1461892

Hom.:

108

Cov.:

AF XY:

0.0109

AC XY:

7947

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00191

Gnomad4 AMR exome

AF:

0.00503

Gnomad4 ASJ exome

AF:

0.00333

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000638

Gnomad4 FIN exome

AF:

0.0150

Gnomad4 NFE exome

AF:

0.0130

Gnomad4 OTH exome

AF:

0.00841

GnomAD4 genome

AF:

0.00817

AC:

1244

AN:

152256

Hom.:

Cov.:

AF XY:

0.00815

AC XY:

607

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0169

Gnomad4 NFE

AF:

0.0126

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.0114

Hom.:

Bravo

AF:

0.00723

TwinsUK

AF:

0.0135

AC:

ALSPAC

AF:

0.0148

AC:

ESP6500AA

AF:

0.00169

AC:

ESP6500EA

AF:

0.0130

AC:

110

ExAC

AF:

0.00853

AC:

1033

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0123

EpiControl

AF:

0.0123

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

SERPINA9: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.67

T;T;T;T

MetaRNN

Benign

0.0050

T;T;T;T

MetaSVM

Uncertain

-0.24

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-7.7

D;D;D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D

Polyphen

1.0

D;P;P;D

Vest4

0.15

MVP

0.79

MPC

0.040

ClinPred

0.074

GERP RS

3.0

Varity_R

0.26

gMVP

0.15

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