NM_052839.4:c.1177G>T

Variant names:

• chr22-50177889-G-T
• rs747245861
• NM_052839.4:c.1177G>T

Variant summary

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

The NM_052839.4(PANX2):​c.1177G>T​(p.Ala393Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PANX2 NM_052839.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.69

Genes affected

PANX2 (HGNC:8600): (pannexin 2) 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 1 are abundantly expressed in central nervous system (CNS) and are coexpressed in various neuronal populations. Studies in Xenopus oocytes suggest that this protein alone and in combination with pannexin 1 may form cell type-specific gap junctions with distinct properties. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

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=0.107933104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANX2	NM_052839.4	c.1177G>T	p.Ala393Ser	missense_variant	Exon 2 of 3	ENST00000395842.3	NP_443071.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANX2	ENST00000395842.3	c.1177G>T	p.Ala393Ser	missense_variant	Exon 2 of 3	2	NM_052839.4	ENSP00000379183.2
PANX2	ENST00000159647.9	c.1177G>T	p.Ala393Ser	missense_variant	Exon 2 of 4	1		ENSP00000159647.5
PANX2	ENST00000402472.2	n.*964G>T		non_coding_transcript_exon_variant	Exon 3 of 5	2		ENSP00000384148.2
PANX2	ENST00000402472.2	n.*964G>T		3_prime_UTR_variant	Exon 3 of 5	2		ENSP00000384148.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1390112 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 686556

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	.;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.42	N;N
REVEL	Benign	0.029
Sift	Benign	0.058	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.017	B;B
Vest4		0.13
MutPred		0.19		Gain of glycosylation at A393 (P = 0.0426);Gain of glycosylation at A393 (P = 0.0426);
MVP		0.055
MPC		1.9
ClinPred		0.76	D
GERP RS		3.3
Varity_R		0.056
gMVP		0.56

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: rs747245861; hg19: chr22-50616318;