Genetic Variant PANX1:p.Leu115Phe (chr11-94178390-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015368.4(PANX1):c.343C>T(p.Leu115Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,722 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L115V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PANX1
NM_015368.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.29

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANX1	NM_015368.4 link	c.343C>T	p.Leu115Phe	missense_variant	Exon 3 of 5	ENST00000227638.8	NP_056183.2	Q96RD7-1A0A024R397
PANX1	XM_011542734.3 link	c.-84C>T		5_prime_UTR_variant	Exon 4 of 6		XP_011541036.1
PANX1	XM_047426702.1 link	c.-84C>T		5_prime_UTR_variant	Exon 3 of 5		XP_047282658.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANX1	ENST00000227638.8 link	c.343C>T	p.Leu115Phe	missense_variant	Exon 3 of 5	1	NM_015368.4	ENSP00000227638.3		Q96RD7-1
PANX1	ENST00000436171.2 link	c.343C>T	p.Leu115Phe	missense_variant	Exon 3 of 5	1		ENSP00000411461.2		Q96RD7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461722

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727166

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111872

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.099

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.71

D;D

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.7

M;M

PhyloP100

2.3

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.2

N;N

REVEL

Uncertain

0.33

Sift

Benign

0.044

D;D

Sift4G

Uncertain

0.014

D;D

Polyphen

1.0

D;D

Vest4

0.64

MutPred

0.44

Loss of stability (P = 0.2348);Loss of stability (P = 0.2348);

MVP

0.58

MPC

0.48

ClinPred

0.95

GERP RS

4.4

Varity_R

0.46

gMVP

0.58

Mutation Taster

=37/63

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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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11-94178390-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over