Variant 14-94563894-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006215.4(SERPINA4):c.412C>T(p.Arg138Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000569 in 1,614,172 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00034 ( 1 hom. )

Consequence

SERPINA4
NM_006215.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.143

Variant links:

Genes affected

SERPINA4 (HGNC:8948): (serpin family A member 4) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Located in extracellular exosome. Biomarker of diabetic retinopathy. [provided by Alliance of Genome Resources, Apr 2022]

SERPINA4 links:

SERPINA5 (HGNC:8723): (serpin family A member 5) The protein encoded by this gene is a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. This gene is one in a cluster of serpin genes located on the q arm of chromosome 14. This family member is a glycoprotein that can inhibit several serine proteases, including protein C and various plasminogen activators and kallikreins, and it thus plays diverse roles in hemostasis and thrombosis in multiple organs. [provided by RefSeq, Aug 2012]

SERPINA5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005294293).

BP6

Variant 14-94563894-C-T is Benign according to our data. Variant chr14-94563894-C-T is described in ClinVar as [Benign]. Clinvar id is 787952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SERPINA4	NM_006215.4 linkuse as main transcript	c.412C>T	p.Arg138Cys	missense_variant	2/5	ENST00000557004.6	NP_006206.2
SERPINA4	NM_001289032.2 linkuse as main transcript	c.523C>T	p.Arg175Cys	missense_variant	2/5		NP_001275961.1
SERPINA4	NM_001289033.2 linkuse as main transcript	c.412C>T	p.Arg138Cys	missense_variant	2/5		NP_001275962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINA4	ENST00000557004.6 linkuse as main transcript	c.412C>T	p.Arg138Cys	missense_variant	2/5	1	NM_006215.4	ENSP00000450838	P1

Frequencies

GnomAD3 genomes

AF:

0.00279

AC:

424

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00987

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000939

AC:

236

AN:

251446

Hom.:

AF XY:

0.000765

AC XY:

104

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.0117

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000817

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000339

AC:

495

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000327

AC XY:

238

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0109

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000661

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.00278

AC:

424

AN:

152280

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

207

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00984

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000490

Hom.:

Bravo

AF:

0.00320

ESP6500AA

AF:

0.00999

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00122

AC:

148

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

8.0

DANN

Benign

0.93

DEOGEN2

Uncertain

0.64

D;D;D

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.23

.;.;T

MetaRNN

Benign

0.0053

T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.7

L;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.20

Sift

Benign

0.076

T;T;T

Sift4G

Benign

0.11

T;T;T

Polyphen

0.51

P;P;P

Vest4

0.072

MVP

0.58

MPC

0.065

ClinPred

0.0086

GERP RS

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.19

gMVP

0.26

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