11-94129327-A-C

Position:

• chr11-94129327-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.71 (38363 hom., cov: 33)
  • Exomes 𝑓: 0.64 (301572 hom.)
• Consequence: PANX1 NM_015368.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.261

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PANX1	NM_015368.4	c.15A>C	p.Gln5His	missense_variant	1/5	ENST00000227638.8	NP_056183.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PANX1	ENST00000227638.8	c.15A>C	p.Gln5His	missense_variant	1/5	1	NM_015368.4	ENSP00000227638.3
PANX1	ENST00000436171.2	c.15A>C	p.Gln5His	missense_variant	1/5	1		ENSP00000411461.2

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107241 AN: 152070 Hom.: 38303 Cov.: 33

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

GnomAD3 exomes AF: 0.676 AC: 167592 AN: 247922 Hom.: 57570 AF XY: 0.665 AC XY: 89271 AN XY: 134286

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 SAS exome AF: 0.610

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.: 43 AF XY: 0.639 AC XY: 462988 AN XY: 724502

Gnomad4 AFR exome AF: 0.831

Gnomad4 AMR exome AF: 0.822

Gnomad4 ASJ exome AF: 0.701

Gnomad4 EAS exome AF: 0.666

Gnomad4 SAS exome AF: 0.609

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.626

Gnomad4 OTH exome AF: 0.652

GnomAD4 genome AF: 0.705 AC: 107361 AN: 152188 Hom.: 38363 Cov.: 33 AF XY: 0.706 AC XY: 52494 AN XY: 74398

Gnomad4 AFR AF: 0.827

Gnomad4 AMR AF: 0.779

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.687

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.728

Alfa AF: 0.653 Hom.: 72830

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 29, 2019	This variant is associated with the following publications: (PMID: 25947940) -

Oocyte maturation defect 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.034
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.80
DEOGEN2	Benign	0.035	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.49	T;T
MetaRNN	Benign	8.7e-7	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-2.0	N;N
PrimateAI	Uncertain	0.76	T
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	T
GERP RS		3.3
Varity_R		0.12
gMVP		0.64

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

LitVar

Other links and lift over

dbSNP: rs1138800; hg19: chr11-93862493; COSMIC: COSV57132946;