NM_015368.4:c.343C>T

Variant names:

• chr11-94178390-C-T
• NM_015368.4:c.343C>T

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PANX1 NM_015368.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29

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 Uncertain_significance. Variant got 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	c.343C>T	p.Leu115Phe	missense_variant	Exon 3 of 5	ENST00000227638.8	NP_056183.2
PANX1	XM_011542734.3	c.-84C>T		5_prime_UTR_variant	Exon 4 of 6		XP_011541036.1
PANX1	XM_047426702.1	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	c.343C>T	p.Leu115Phe	missense_variant	Exon 3 of 5	1	NM_015368.4	ENSP00000227638.3
PANX1	ENST00000436171.2	c.343C>T	p.Leu115Phe	missense_variant	Exon 3 of 5	1		ENSP00000411461.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461722 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727166

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.099
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Uncertain	0.67	T
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	D
GERP RS		4.4
Varity_R		0.46
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-93911556;