11-94129327-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015368.4(PANX1):c.15A>C(p.Gln5His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 1,609,576 control chromosomes in the GnomAD database, including 339,935 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 38363 hom., cov: 33)

Exomes 𝑓: 0.64 ( 301572 hom. )

Consequence

PANX1
NM_015368.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.261

Publications

51 publications found

Variant links:

Genes affected

PANX1 (HGNC:8599): (pannexin 1) The protein encoded by this gene belongs to the innexin family. Innexin family members are the structural components of gap junctions. This protein and pannexin 2 are abundantly expressed in central nerve system (CNS) and are coexpressed in various neuronal populations. Studies in Xenopus oocytes suggest that this protein alone and in combination with pannexin 2 may form cell type-specific gap junctions with distinct properties. [provided by RefSeq, Jul 2008]

PANX1 Gene-Disease associations (from GenCC):

oocyte maturation defect 7
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

PANX1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.693942E-7).

BP6

Variant 11-94129327-A-C is Benign according to our data. Variant chr11-94129327-A-C is described in ClinVar as [Benign]. Clinvar id is 1254433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANX1	NM_015368.4 link	c.15A>C	p.Gln5His	missense_variant	Exon 1 of 5	ENST00000227638.8	NP_056183.2	Q96RD7-1A0A024R397

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANX1	ENST00000227638.8 link	c.15A>C	p.Gln5His	missense_variant	Exon 1 of 5	1	NM_015368.4	ENSP00000227638.3		Q96RD7-1
PANX1	ENST00000436171.2 link	c.15A>C	p.Gln5His	missense_variant	Exon 1 of 5	1		ENSP00000411461.2		Q96RD7-2

Frequencies

GnomAD3 genomes

AF:

0.705

AC:

107241

AN:

152070

Hom.:

38303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.827

Gnomad AMI

AF:

0.635

Gnomad AMR

AF:

0.778

Gnomad ASJ

AF:

0.711

Gnomad EAS

AF:

0.637

Gnomad SAS

AF:

0.597

Gnomad FIN

AF:

0.687

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.631

Gnomad OTH

AF:

0.726

GnomAD2 exomes

AF:

0.676

AC:

167592

AN:

247922

AF XY:

0.665

show subpopulations

Gnomad AFR exome

AF:

0.829

Gnomad AMR exome

AF:

0.830

Gnomad ASJ exome

AF:

0.701

Gnomad EAS exome

AF:

0.633

Gnomad FIN exome

AF:

0.674

Gnomad NFE exome

AF:

0.630

Gnomad OTH exome

AF:

0.667

GnomAD4 exome

AF:

0.641

AC:

934571

AN:

1457388

Hom.:

301572

Cov.:

AF XY:

0.639

AC XY:

462988

AN XY:

724502

show subpopulations

African (AFR)

AF:

0.831

AC:

27728

AN:

33380

American (AMR)

AF:

0.822

AC:

36620

AN:

44548

Ashkenazi Jewish (ASJ)

AF:

0.701

AC:

18272

AN:

26078

East Asian (EAS)

AF:

0.666

AC:

26263

AN:

39452

South Asian (SAS)

AF:

0.609

AC:

52358

AN:

85942

European-Finnish (FIN)

AF:

0.667

AC:

35522

AN:

53278

Middle Eastern (MID)

AF:

0.699

AC:

4024

AN:

5754

European-Non Finnish (NFE)

AF:

0.626

AC:

694556

AN:

1108780

Other (OTH)

AF:

0.652

AC:

39228

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

16373

32746

49118

65491

81864

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.705

AC:

107361

AN:

152188

Hom.:

38363

Cov.:

AF XY:

0.706

AC XY:

52494

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.827

AC:

34337

AN:

41542

American (AMR)

AF:

0.779

AC:

11919

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.711

AC:

2468

AN:

3472

East Asian (EAS)

AF:

0.638

AC:

3279

AN:

5142

South Asian (SAS)

AF:

0.598

AC:

2886

AN:

4824

European-Finnish (FIN)

AF:

0.687

AC:

7275

AN:

10592

Middle Eastern (MID)

AF:

0.629

AC:

185

AN:

294

European-Non Finnish (NFE)

AF:

0.631

AC:

42897

AN:

67996

Other (OTH)

AF:

0.728

AC:

1537

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1608

3215

4823

6430

8038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.659

Hom.:

153664

Bravo

AF:

0.722

TwinsUK

AF:

0.628

AC:

2329

ALSPAC

AF:

0.642

AC:

2473

ESP6500AA

AF:

0.819

AC:

3607

ESP6500EA

AF:

0.640

AC:

5502

ExAC

AF:

0.668

AC:

81048

Asia WGS

AF:

0.659

AC:

2294

AN:

3478

EpiCase

AF:

0.640

EpiControl

AF:

0.641

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 29, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 25947940) -

Oocyte maturation defect 7

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.034

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.035

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.49

T;T

MetaRNN

Benign

8.7e-7

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.0

N;N

PhyloP100

0.26

PrimateAI

Uncertain

0.76

PROVEAN

Benign

2.5

N;N

REVEL

Benign

0.032

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.034

MutPred

0.39

Loss of catalytic residue at Q5 (P = 0.0251);Loss of catalytic residue at Q5 (P = 0.0251);

MPC

0.078

ClinPred

0.0028

GERP RS

3.3

PromoterAI

-0.26

Neutral

(source)

Varity_R

0.12

gMVP

0.64

Mutation Taster

=96/4

polymorphism (auto)

(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

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11-94129327-A-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over