rs139624657

chr19-40394272-TTCCTCCTCCTCC-Tchr19-40394272-TTCCTCCTCCTCC-TTCCchr19-40394272-TTCCTCCTCCTCC-TTCCTCCchr19-40394272-TTCCTCCTCCTCC-TTCCTCCTCCchr19-40394272-TTCCTCCTCCTCC-TTCCTCCTCCTCCTCCchr19-40394272-TTCCTCCTCCTCC-TTCCTCCTCCTCCTCCTCCchr19-40394272-TTCCTCCTCCTCC-TTCCTCCTCCTCCTCCTCCTCCchr19-40394272-TTCCTCCTCCTCC-TTCCTCCTCCTCCTCCTCCTCCTCCTCC

Variant summary

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

The NM_181882.3(PRX):c.4068_4079del(p.Glu1358_Glu1361del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 151,214 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: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: PRX NM_181882.3 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

Genes affected

PRX (HGNC:13797): (periaxin) This gene encodes a protein involved in peripheral nerve myelin upkeep. The encoded protein contains 2 PDZ domains which were named after PSD95 (post synaptic density protein), DlgA (Drosophila disc large tumor suppressor), and ZO1 (a mammalian tight junction protein). Two alternatively spliced transcript variants have been described for this gene which encode different protein isoforms and which are targeted differently in the Schwann cell. Mutations in this gene cause Charcot-Marie-Tooth neuoropathy, type 4F and Dejerine-Sottas neuropathy. [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/exons	MANE	UniProt
PRX	NM_181882.3	c.4068_4079del	p.Glu1358_Glu1361del	inframe_deletion	7/7	ENST00000324001.8
PRX	NM_001411127.1	c.4353_4364del	p.Glu1453_Glu1456del	inframe_deletion	7/7
PRX	XM_017027047.2	c.3966_3977del	p.Glu1324_Glu1327del	inframe_deletion	4/4
PRX	NM_020956.2	c.*4273_*4284del		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRX	ENST00000324001.8	c.4068_4079del	p.Glu1358_Glu1361del	inframe_deletion	7/7	1	NM_181882.3	A2

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151214 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73800

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs139624657; hg19: chr19-40900179;