Variant chr19-2254193-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144616.4(JSRP1):c.256G>A(p.Gly86Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000656 in 1,601,436 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

JSRP1
NM_144616.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.871

Variant links:

Genes affected

JSRP1 (HGNC:24963): (junctional sarcoplasmic reticulum protein 1) The protein encoded by this gene is involved in excitation-contraction coupling at the sarcoplasmic reticulum. The encoded protein can interact with CACNA1S, CACNB1, and calsequestrin to help regulate calcium influx and efflux in skeletal muscle. [provided by RefSeq, Jul 2012]

JSRP1 links:

JSRP1 (HGNC:):

JSRP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06888029).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JSRP1	NM_144616.4 linkuse as main transcript	c.256G>A	p.Gly86Arg	missense_variant	4/7	ENST00000300961.10	NP_653217.1	Q96MG2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JSRP1	ENST00000300961.10 linkuse as main transcript	c.256G>A	p.Gly86Arg	missense_variant	4/7	2	NM_144616.4	ENSP00000300961.4		Q96MG2
JSRP1	ENST00000593238.2 linkuse as main transcript	n.712G>A		non_coding_transcript_exon_variant	4/5	5

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00307

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000291

AC:

AN:

240204

Hom.:

AF XY:

0.0000539

AC XY:

AN XY:

129852

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000915

Gnomad ASJ exome

AF:

0.000109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000517

GnomAD4 exome

AF:

0.0000352

AC:

AN:

1449118

Hom.:

Cov.:

AF XY:

0.0000319

AC XY:

AN XY:

720450

show subpopulations

Gnomad4 AFR exome

AF:

0.0000606

Gnomad4 AMR exome

AF:

0.000444

Gnomad4 ASJ exome

AF:

0.000316

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000723

Gnomad4 OTH exome

AF:

0.000217

GnomAD4 genome

AF:

0.000355

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000309

Hom.:

Bravo

AF:

0.000914

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2023

The c.256G>A (p.G86R) alteration is located in exon 4 (coding exon 3) of the JSRP1 gene. This alteration results from a G to A substitution at nucleotide position 256, causing the glycine (G) at amino acid position 86 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.65

M_CAP

Benign

0.037

MetaRNN

Benign

0.069

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

MutationTaster

Benign

0.98

N;N

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.10

Sift

Uncertain

0.013

Sift4G

Benign

0.069

Polyphen

1.0

Vest4

0.34

MutPred

0.15

Gain of methylation at G86 (P = 0.023);

MVP

0.37

MPC

0.24

ClinPred

0.64

GERP RS

3.5

Varity_R

0.15

gMVP

0.026

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