chr11-124617384-C-A

Variant names:

• chr11-124617384-C-A
• rs201186259
• NM_052959.3:c.435C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052959.3(PANX3):​c.435C>A​(p.Ser145Arg) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S145S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PANX3 NM_052959.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.78

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]

LOC124902779 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18010554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANX3	NM_052959.3	c.435C>A	p.Ser145Arg	missense_variant	Exon 3 of 4	ENST00000284288.3	NP_443191.1
LOC124902779	XR_007062932.1	n.5818G>T		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	c.435C>A	p.Ser145Arg	missense_variant	Exon 3 of 4	1	NM_052959.3	ENSP00000284288.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.2
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.043	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.10
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.016	D
Polyphen		0.014	B
Vest4		0.40
MutPred		0.33		Gain of MoRF binding (P = 0.0241);
MVP		0.20
MPC		0.28
ClinPred		0.24	T
GERP RS		-9.8
Varity_R		0.33
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs201186259; hg19: chr11-124487280;