Genetic Variant SERPINA11:p.Val242Ile (chr14-94446524-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_001080451.2(SERPINA11):c.724G>A(p.Val242Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,986 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SERPINA11
NM_001080451.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.511

Publications

0 publications found

Variant links:

Genes affected

SERPINA11 (HGNC:19193): (serpin family A member 11) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SERPINA11 Gene-Disease associations (from GenCC):

hydrops fetalis
Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

SERPINA11 links:

ENSG00000256357 (HGNC:):

ENSG00000256357 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 14-94446524-C-T is Benign according to our data. Variant chr14-94446524-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2569994.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080451.2. 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
	SERPINA11	NM_001080451.2	MANE Select	c.724G>A	p.Val242Ile	missense	Exon 3 of 5	NP_001073920.1	Q86U17
	SERPINA11	NM_001429948.1		c.112G>A	p.Val38Ile	missense	Exon 3 of 5	NP_001416877.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINA11	ENST00000334708.4	TSL:1 MANE Select	c.724G>A	p.Val242Ile	missense	Exon 3 of 5	ENSP00000335024.3	Q86U17
SERPINA11	ENST00000850861.1		c.733G>A	p.Val245Ile	missense	Exon 3 of 5	ENSP00000520948.1	A0ABJ7H2Z4
SERPINA11	ENST00000905969.1		c.724G>A	p.Val242Ile	missense	Exon 3 of 5	ENSP00000576028.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

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

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461790

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727196

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111916

Other (OTH)

AF:

0.0000331

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

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:

0.0000197

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41452

American (AMR)

AF:

0.000131

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.0000301

Hom.:

Bravo

AF:

0.0000529

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Benign

7.4

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.62

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.48

MetaSVM

Uncertain

0.045

MutationAssessor

Uncertain

2.1

PhyloP100

0.51

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.70

REVEL

Uncertain

0.29

Sift

Benign

0.21

Sift4G

Benign

0.23

Polyphen

0.59

Vest4

0.068

MutPred

0.84

Loss of catalytic residue at V242 (P = 0.0688)

MVP

0.29

MPC

0.046

ClinPred

0.29

GERP RS

0.19

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.056

gMVP

0.16

Mutation Taster

=98/2

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