rs777413169

Variant names:

• chr19-40396372-C-A
• rs777413169
• NM_181882.3:c.1980G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-40396372-C-A
• chr19-40396372-C-T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_181882.3(PRX):​c.1980G>T​(p.Pro660Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,611,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P660P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: PRX NM_181882.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.13
• Publications: 0 publications found

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]

PRX Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease type 4

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Charcot-Marie-Tooth disease type 4F

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• Charcot-Marie-Tooth disease type 3

  Inheritance: AD, AR Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 19-40396372-C-A is Benign according to our data. Variant chr19-40396372-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 698451.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.14 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRX	NM_181882.3	c.1980G>T	p.Pro660Pro	synonymous_variant	Exon 7 of 7	ENST00000324001.8	NP_870998.2
PRX	NM_001411127.1	c.2265G>T	p.Pro755Pro	synonymous_variant	Exon 7 of 7		NP_001398056.1
PRX	XM_017027047.2	c.1878G>T	p.Pro626Pro	synonymous_variant	Exon 4 of 4		XP_016882536.1
PRX	NM_020956.2	c.*2185G>T		3_prime_UTR_variant	Exon 6 of 6		NP_066007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRX	ENST00000324001.8	c.1980G>T	p.Pro660Pro	synonymous_variant	Exon 7 of 7	1	NM_181882.3	ENSP00000326018.6

Frequencies

GnomAD3 genomes AF: 0.0000266 AC: 4 AN: 150472 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000245

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: 0.0000444

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251024 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000178 AC: 26 AN: 1461144 Hom.: 0 Cov.: 37 AF XY: 0.0000151 AC XY: 11 AN XY: 726918

African (AFR) AF: 0.00 AC: 0 AN: 32988

American (AMR) AF: 0.00 AC: 0 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111948

Other (OTH) AF: 0.0000332 AC: 2 AN: 60326

GnomAD4 genome AF: 0.0000266 AC: 4 AN: 150472 Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1 AN XY: 73388

African (AFR) AF: 0.0000245 AC: 1 AN: 40772

American (AMR) AF: 0.00 AC: 0 AN: 15110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5110

South Asian (SAS) AF: 0.00 AC: 0 AN: 4720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000444 AC: 3 AN: 67614

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000302

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Charcot-Marie-Tooth disease type 4 Benign:1

Jul 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.015
DANN	Benign	0.63
PhyloP100		-4.1

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: rs777413169; hg19: chr19-40902279;