14-94614514-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001085.5(SERPINA3):c.73C>T(p.Pro25Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,613,914 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 2 hom. )

Consequence

SERPINA3
NM_001085.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.316

Publications

3 publications found

Variant links:

Genes affected

SERPINA3 (HGNC:16): (serpin family A member 3) 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. Polymorphisms in this protein appear to be tissue specific and influence protease targeting. Variations in this protein's sequence have been implicated in Alzheimer's disease, and deficiency of this protein has been associated with liver disease. Mutations have been identified in patients with Parkinson disease and chronic obstructive pulmonary disease. [provided by RefSeq, Jun 2020]

SERPINA3 links:

ENSG00000273259 (HGNC:):

ENSG00000273259 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023804158).

BP6

Variant 14-94614514-C-T is Benign according to our data. Variant chr14-94614514-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2644481.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINA3	NM_001085.5	MANE Select	c.73C>T	p.Pro25Ser	missense	Exon 2 of 5	NP_001076.2	P01011-1
SERPINA3	NM_001384672.1		c.73C>T	p.Pro25Ser	missense	Exon 2 of 5	NP_001371601.1	P01011-1
SERPINA3	NM_001384673.1		c.73C>T	p.Pro25Ser	missense	Exon 3 of 6	NP_001371602.1	P01011-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINA3	ENST00000393078.5	TSL:1 MANE Select	c.73C>T	p.Pro25Ser	missense	Exon 2 of 5	ENSP00000376793.3	P01011-1
SERPINA3	ENST00000393080.8	TSL:1	c.73C>T	p.Pro25Ser	missense	Exon 2 of 5	ENSP00000376795.4	P01011-1
ENSG00000273259	ENST00000553947.1	TSL:2	n.*899C>T		non_coding_transcript_exon	Exon 5 of 8	ENSP00000452367.2	G3V5I3

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000485

AC:

122

AN:

251308

AF XY:

0.000626

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00328

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000298

AC:

436

AN:

1461674

Hom.:

Cov.:

AF XY:

0.000378

AC XY:

275

AN XY:

727090

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00222

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00188

AC:

162

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000161

AC:

179

AN:

1111818

Other (OTH)

AF:

0.000397

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

118

148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000204

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41524

American (AMR)

AF:

0.0000654

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00124

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68020

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000503

Hom.:

Bravo

AF:

0.000261

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000445

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

SERPINA3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.34

CADD

Benign

4.3

(source)

DANN

Benign

0.96

DEOGEN2

Uncertain

0.49

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.45

M_CAP

Benign

0.027

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.38

MutationAssessor

Benign

1.9

PhyloP100

-0.32

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-4.8

REVEL

Benign

0.15

Sift

Benign

0.082

Sift4G

Benign

0.12

Polyphen

0.096

Vest4

0.11

MVP

0.92

MPC

0.013

ClinPred

0.047

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.069

gMVP

0.13

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over