Variant 12-49295552-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006262.4(PRPH):c.352C>A(p.Leu118Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,580,860 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 3 hom. )

Consequence

PRPH
NM_006262.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.693

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]

PRPH links:

TROAP-AS1 (HGNC:55453): (TROAP and PRPH antisense RNA 1)

TROAP-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0112890005).

BP6

Variant 12-49295552-C-A is Benign according to our data. Variant chr12-49295552-C-A is described in ClinVar as [Benign]. Clinvar id is 737329.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPH	NM_006262.4 linkuse as main transcript	c.352C>A	p.Leu118Met	missense_variant	1/9	ENST00000257860.9	NP_006253.2
TROAP-AS1	NR_120449.1 linkuse as main transcript	n.2520G>T		non_coding_transcript_exon_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPH	ENST00000257860.9 linkuse as main transcript	c.352C>A	p.Leu118Met	missense_variant	1/9	1	NM_006262.4	ENSP00000257860	P1	P41219-1
TROAP-AS1	ENST00000553259.1 linkuse as main transcript	n.2520G>T		non_coding_transcript_exon_variant	6/8	2
PRPH	ENST00000451891.4 linkuse as main transcript	c.99+10C>A		intron_variant		5		ENSP00000408897

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00712

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000532

AC:

100

AN:

187912

Hom.:

AF XY:

0.000482

AC XY:

AN XY:

101666

show subpopulations

Gnomad AFR exome

AF:

0.0000919

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00675

Gnomad SAS exome

AF:

0.0000397

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000401

GnomAD4 exome

AF:

0.000115

AC:

164

AN:

1428480

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

707532

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.0000507

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00340

Gnomad4 SAS exome

AF:

0.000134

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.13e-7

Gnomad4 OTH exome

AF:

0.000321

GnomAD4 genome

AF:

0.000263

AC:

AN:

152380

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74524

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00713

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.000212

ExAC

AF:

0.000393

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.83

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.011

MetaSVM

Pathogenic

0.99

MutationAssessor

Pathogenic

4.4

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-1.7

REVEL

Pathogenic

0.69

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.69

MutPred

0.70

Gain of ubiquitination at K114 (P = 0.0582);

MVP

0.87

MPC

1.5

ClinPred

0.29

GERP RS

2.6

Varity_R

0.76

gMVP

0.65

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over