chr11-94178393-T-C

Variant names:

• chr11-94178393-T-C
• rs139198736
• NM_015368.4:c.346T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015368.4(PANX1):​c.346T>C​(p.Phe116Leu) 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. 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. F116V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PANX1 NM_015368.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.607
• Publications: 0 publications found

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)

ACMG classification

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=0.052937716).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015368.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANX1	NM_015368.4	MANE Select	c.346T>C	p.Phe116Leu	missense	Exon 3 of 5	NP_056183.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANX1	ENST00000227638.8	TSL:1 MANE Select	c.346T>C	p.Phe116Leu	missense	Exon 3 of 5	ENSP00000227638.3	Q96RD7-1
	PANX1	ENST00000436171.2	TSL:1	c.346T>C	p.Phe116Leu	missense	Exon 3 of 5	ENSP00000411461.2	Q96RD7-2
	PANX1	ENST00000931248.1		c.394T>C	p.Phe132Leu	missense	Exon 3 of 5	ENSP00000601307.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.6
DANN	Benign	0.30
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.61
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.034
Sift	Benign	0.96	T
Sift4G	Benign	0.53	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.39		Gain of catalytic residue at F116 (P = 0.0515)
MVP		0.099
MPC		0.096
ClinPred		0.069	T
GERP RS		0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.16
gMVP		0.48
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs139198736; hg19: chr11-93911559;