Genetic Variant PANX1:c.-459C>T (chr11-94128854-C-T) – ACMG Classification: Benign (-20 pts)

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.-459C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 152,560 control chromosomes in the GnomAD database, including 19,733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 19674 hom., cov: 34)

Exomes 𝑓: 0.47 ( 59 hom. )

Consequence

PANX1
NM_015368.4 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.323

Publications

11 publications found

Variant links:

COSMIC-nc: COSV57134697

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 (BayesDel_noAF=-0.51).

BP6

Variant 11-94128854-C-T is Benign according to our data. Variant chr11-94128854-C-T is described in ClinVar as [Benign]. Clinvar id is 1228505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANX1	NM_015368.4 link	c.-459C>T		5_prime_UTR_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.-459C>T		5_prime_UTR_variant	Exon 1 of 5	1	NM_015368.4	ENSP00000227638.3		Q96RD7-1
PANX1	ENST00000436171.2 link	c.-459C>T		upstream_gene_variant		1		ENSP00000411461.2		Q96RD7-2

Frequencies

GnomAD3 genomes

AF:

0.506

AC:

76895

AN:

152004

Hom.:

19659

Cov.:

show subpopulations

Gnomad AFR

AF:

0.456

Gnomad AMI

AF:

0.572

Gnomad AMR

AF:

0.597

Gnomad ASJ

AF:

0.597

Gnomad EAS

AF:

0.442

Gnomad SAS

AF:

0.466

Gnomad FIN

AF:

0.593

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.503

Gnomad OTH

AF:

0.549

GnomAD4 exome

AF:

0.466

AC:

204

AN:

438

Hom.:

AF XY:

0.466

AC XY:

110

AN XY:

236

show subpopulations

African (AFR)

AF:

0.542

AC:

AN:

American (AMR)

AF:

0.583

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.286

AC:

AN:

South Asian (SAS)

AF:

0.600

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.455

AC:

151

AN:

332

Other (OTH)

AF:

0.450

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.506

AC:

76957

AN:

152122

Hom.:

19674

Cov.:

AF XY:

0.509

AC XY:

37882

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.456

AC:

18945

AN:

41520

American (AMR)

AF:

0.597

AC:

9145

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.597

AC:

2071

AN:

3470

East Asian (EAS)

AF:

0.443

AC:

2277

AN:

5142

South Asian (SAS)

AF:

0.467

AC:

2254

AN:

4822

European-Finnish (FIN)

AF:

0.593

AC:

6285

AN:

10596

Middle Eastern (MID)

AF:

0.503

AC:

146

AN:

290

European-Non Finnish (NFE)

AF:

0.503

AC:

34160

AN:

67966

Other (OTH)

AF:

0.549

AC:

1159

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2024

4048

6072

8096

10120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.502

Hom.:

6353

Bravo

AF:

0.511

Asia WGS

AF:

0.457

AC:

1594

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

0.32

PromoterAI

0.30

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr11-94128854-C-T

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