dbSNP rs1243007812: PANX3:p.Ala135Ser (chr11-124617352-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_052959.3(PANX3):c.403G>T(p.Ala135Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PANX3
NM_052959.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

Publications

0 publications found

Variant links:

Genes affected

PANX3 (HGNC:20573): (pannexin 3) The protein encoded by this gene belongs to the innexin family. Innexin family members are known to be the structural components of gap junctions. [provided by RefSeq, Jul 2008]

PANX3 links:

LOC124902779 (HGNC:):

LOC124902779 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030564487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANX3	NM_052959.3 link	c.403G>T	p.Ala135Ser	missense_variant	Exon 3 of 4	ENST00000284288.3	NP_443191.1	Q96QZ0
LOC124902779	XR_007062932.1 link	n.5850C>A		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANX3	ENST00000284288.3 link	c.403G>T	p.Ala135Ser	missense_variant	Exon 3 of 4	1	NM_052959.3	ENSP00000284288.2		Q96QZ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460732

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726728

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52304

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111986

Other (OTH)

AF:

0.00

AC:

AN:

60388

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 10, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.403G>T (p.A135S) alteration is located in exon 3 (coding exon 3) of the PANX3 gene. This alteration results from a G to T substitution at nucleotide position 403, causing the alanine (A) at amino acid position 135 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.0025

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.65

M_CAP

Benign

0.0093

MetaRNN

Benign

0.031

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.40

PhyloP100

1.7

PrimateAI

Benign

0.36

PROVEAN

Benign

0.54

REVEL

Benign

0.029

Sift

Benign

0.77

Sift4G

Benign

0.70

Polyphen

0.0010

Vest4

0.25

MutPred

0.28

Loss of helix (P = 0.0626);

MVP

0.030

MPC

0.13

ClinPred

0.042

GERP RS

2.8

Varity_R

0.036

gMVP

0.34

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over