Variant 8-74244914-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_020647.4(JPH1):c.1520C>T(p.Thr507Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,614,112 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 5 hom. )

Consequence

JPH1
NM_020647.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.190

Variant links:

Genes affected

JPH1 (HGNC:14201): (junctophilin 1) Junctional complexes between the plasma membrane and endoplasmic/sarcoplasmic reticulum are a common feature of all excitable cell types and mediate cross talk between cell surface and intracellular ion channels. The protein encoded by this gene is a component of junctional complexes and is composed of a C-terminal hydrophobic segment spanning the endoplasmic/sarcoplasmic reticulum membrane and a remaining cytoplasmic domain that shows specific affinity for the plasma membrane. This gene is a member of the junctophilin gene family. [provided by RefSeq, Jul 2008]

JPH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038918555).

BP6

Variant 8-74244914-G-A is Benign according to our data. Variant chr8-74244914-G-A is described in ClinVar as [Benign]. Clinvar id is 3033657.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 433 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JPH1	NM_020647.4 linkuse as main transcript	c.1520C>T	p.Thr507Met	missense_variant	4/6	ENST00000342232.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JPH1	ENST00000342232.5 linkuse as main transcript	c.1520C>T	p.Thr507Met	missense_variant	4/6	1	NM_020647.4	P1
JPH1	ENST00000519947.1 linkuse as main transcript	c.*915C>T		3_prime_UTR_variant, NMD_transcript_variant	4/5	1

Frequencies

GnomAD3 genomes

AF:

0.00285

AC:

433

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00171

AC:

431

AN:

251412

Hom.:

AF XY:

0.00147

AC XY:

200

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00720

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00407

Gnomad NFE exome

AF:

0.00164

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.00140

AC:

2049

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

983

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00783

Gnomad4 AMR exome

AF:

0.000827

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00419

Gnomad4 NFE exome

AF:

0.00130

Gnomad4 OTH exome

AF:

0.00119

GnomAD4 genome

AF:

0.00284

AC:

433

AN:

152230

Hom.:

Cov.:

AF XY:

0.00277

AC XY:

206

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00725

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00292

Gnomad4 NFE

AF:

0.00125

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00143

Hom.:

Bravo

AF:

0.00300

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00635

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.00185

AC:

225

EpiCase

AF:

0.00120

EpiControl

AF:

0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

JPH1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 11, 2019

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

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.0

DANN

Benign

0.94

DEOGEN2

Benign

0.15

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.61

M_CAP

Benign

0.0080

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.95

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.70

REVEL

Benign

0.071

Sift

Benign

0.073

Sift4G

Benign

0.12

Polyphen

0.0

Vest4

0.12

MVP

0.17

MPC

0.096

ClinPred

0.0020

GERP RS

-2.2

Varity_R

0.015

gMVP

0.31

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