dbSNP rs28929488: SERPINA6:p.Asp389Asn (chr14-94304471-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PP5BP4

The NM_001756.4(SERPINA6):c.1165G>A(p.Asp389Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000358 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

SERPINA6
NM_001756.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:5U:3

Conservation

PhyloP100: 3.96

Publications

17 publications found

Variant links:

Genes affected

SERPINA6 (HGNC:1540): (serpin family A member 6) This gene encodes an alpha-globulin protein with corticosteroid-binding properties. This is the major transport protein for glucorticoids and progestins in the blood of most vertebrates. The gene localizes to a chromosomal region containing several closely related serine protease inhibitors which may have evolved by duplication events. [provided by RefSeq, Jul 2008]

SERPINA6 Gene-Disease associations (from GenCC):

corticosteroid-binding globulin deficiency
Inheritance: AR, AD, SD, Unknown Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, Orphanet

SERPINA6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PP5

Variant 14-94304471-C-T is Pathogenic according to our data. Variant chr14-94304471-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 16975.

BP4

Computational evidence support a benign effect (MetaRNN=0.013436496). . Strength limited to SUPPORTING due to the PP5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001756.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINA6	NM_001756.4	MANE Select	c.1165G>A	p.Asp389Asn	missense	Exon 5 of 5	NP_001747.3	P08185

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINA6	ENST00000341584.4	TSL:1 MANE Select	c.1165G>A	p.Asp389Asn	missense	Exon 5 of 5	ENSP00000342850.3	P08185
SERPINA6	ENST00000874318.1		c.1336G>A	p.Asp446Asn	missense	Exon 5 of 5	ENSP00000544377.1
SERPINA6	ENST00000874321.1		c.1258G>A	p.Asp420Asn	missense	Exon 6 of 6	ENSP00000544380.1

Frequencies

GnomAD3 genomes

AF:

0.000507

AC:

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000617

AC:

155

AN:

251322

AF XY:

0.000567

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.00784

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000343

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.000343

AC:

501

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000355

AC XY:

258

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33480

American (AMR)

AF:

0.000715

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00704

AC:

184

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000190

AC:

211

AN:

1112010

Other (OTH)

AF:

0.000778

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

128

160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000506

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41482

American (AMR)

AF:

0.00183

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

67992

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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:

0.000477

Hom.:

Bravo

AF:

0.000612

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000511

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000593

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Corticosteroid-binding globulin deficiency (6)

not provided (1)

SERPINA6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.66

Eigen

Benign

-0.088

Eigen_PC

Benign

-0.18

FATHMM_MKL

Pathogenic

0.97

M_CAP

Uncertain

0.097

MetaRNN

Benign

0.013

MetaSVM

Uncertain

0.29

MutationAssessor

Uncertain

2.2

PhyloP100

4.0

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.52

Sift

Benign

0.37

Sift4G

Benign

0.15

Polyphen

0.98

Vest4

0.36

MVP

0.91

MPC

0.45

ClinPred

0.17

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.73

gMVP

0.68

Mutation Taster

=74/26

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