12-49295263-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_006262.4(PRPH):​c.63C>T​(p.Phe21Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 1,611,846 control chromosomes in the GnomAD database, including 306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 37 hom., cov: 33)
Exomes 𝑓: 0.017 ( 269 hom. )

Consequence

PRPH
NM_006262.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -0.0570
Variant links:
Genes affected
PRPH (HGNC:9461): (peripherin) This gene encodes a cytoskeletal protein found in neurons of the peripheral nervous system. The encoded protein is a type III intermediate filament protein with homology to other cytoskeletal proteins such as desmin, and is a different protein that the peripherin found in photoreceptors. Mutations in this gene have been associated with susceptibility to amyotrophic lateral sclerosis. [provided by RefSeq, Jul 2008]
TROAP-AS1 (HGNC:55453): (TROAP and PRPH antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 12-49295263-C-T is Benign according to our data. Variant chr12-49295263-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 66720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.057 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0213 (3246/152336) while in subpopulation EAS AF= 0.0253 (131/5180). AF 95% confidence interval is 0.0237. There are 37 homozygotes in gnomad4. There are 1627 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRPHNM_006262.4 linkc.63C>T p.Phe21Phe synonymous_variant Exon 1 of 9 ENST00000257860.9 NP_006253.2 P41219-1B3KWQ6
TROAP-AS1NR_120449.1 linkn.2809G>A non_coding_transcript_exon_variant Exon 6 of 8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRPHENST00000257860.9 linkc.63C>T p.Phe21Phe synonymous_variant Exon 1 of 9 1 NM_006262.4 ENSP00000257860.4 P41219-1
TROAP-AS1ENST00000553259.1 linkn.2809G>A non_coding_transcript_exon_variant Exon 6 of 8 2
PRPHENST00000451891.4 linkc.-181C>T upstream_gene_variant 5 ENSP00000408897.4 F8W835

Frequencies

GnomAD3 genomes
AF:
0.0211
AC:
3218
AN:
152218
Hom.:
33
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0245
Gnomad AMI
AF:
0.0648
Gnomad AMR
AF:
0.0185
Gnomad ASJ
AF:
0.0423
Gnomad EAS
AF:
0.0254
Gnomad SAS
AF:
0.0188
Gnomad FIN
AF:
0.0431
Gnomad MID
AF:
0.0475
Gnomad NFE
AF:
0.0143
Gnomad OTH
AF:
0.0220
GnomAD3 exomes
AF:
0.0226
AC:
5398
AN:
238442
Hom.:
91
AF XY:
0.0224
AC XY:
2928
AN XY:
130602
show subpopulations
Gnomad AFR exome
AF:
0.0258
Gnomad AMR exome
AF:
0.0248
Gnomad ASJ exome
AF:
0.0303
Gnomad EAS exome
AF:
0.0279
Gnomad SAS exome
AF:
0.0220
Gnomad FIN exome
AF:
0.0457
Gnomad NFE exome
AF:
0.0157
Gnomad OTH exome
AF:
0.0195
GnomAD4 exome
AF:
0.0173
AC:
25235
AN:
1459510
Hom.:
269
Cov.:
31
AF XY:
0.0173
AC XY:
12573
AN XY:
725992
show subpopulations
Gnomad4 AFR exome
AF:
0.0275
Gnomad4 AMR exome
AF:
0.0268
Gnomad4 ASJ exome
AF:
0.0332
Gnomad4 EAS exome
AF:
0.0248
Gnomad4 SAS exome
AF:
0.0221
Gnomad4 FIN exome
AF:
0.0423
Gnomad4 NFE exome
AF:
0.0142
Gnomad4 OTH exome
AF:
0.0213
GnomAD4 genome
AF:
0.0213
AC:
3246
AN:
152336
Hom.:
37
Cov.:
33
AF XY:
0.0218
AC XY:
1627
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.0249
Gnomad4 AMR
AF:
0.0191
Gnomad4 ASJ
AF:
0.0423
Gnomad4 EAS
AF:
0.0253
Gnomad4 SAS
AF:
0.0186
Gnomad4 FIN
AF:
0.0431
Gnomad4 NFE
AF:
0.0143
Gnomad4 OTH
AF:
0.0241
Alfa
AF:
0.0176
Hom.:
23
Bravo
AF:
0.0212
Asia WGS
AF:
0.0480
AC:
168
AN:
3478
EpiCase
AF:
0.0154
EpiControl
AF:
0.0176

ClinVar

Significance: Likely benign
Submissions summary: Benign:3Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2Other:1
Oct 18, 2021
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

-
Epithelial Biology; Institute of Medical Biology, Singapore
Significance: not provided
Review Status: no classification provided
Collection Method: literature only

- -

PRPH-related disorder Benign:1
Feb 21, 2019
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
CADD
Benign
16
DANN
Benign
0.95

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs58403142; hg19: chr12-49689046; API