chr19-2252750-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_144616.4(JSRP1):​c.575G>A​(p.Arg192Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

JSRP1
NM_144616.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.02
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.025383592).
BP6
Variant 19-2252750-C-T is Benign according to our data. Variant chr19-2252750-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3531590.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
JSRP1NM_144616.4 linkc.575G>A p.Arg192Gln missense_variant Exon 7 of 7 ENST00000300961.10 NP_653217.1 Q96MG2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
JSRP1ENST00000300961.10 linkc.575G>A p.Arg192Gln missense_variant Exon 7 of 7 2 NM_144616.4 ENSP00000300961.4 Q96MG2

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152204
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000821
AC:
2
AN:
243592
Hom.:
0
AF XY:
0.0000150
AC XY:
2
AN XY:
133634
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000920
Gnomad OTH exome
AF:
0.000167
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1460212
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
726454
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152204
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.0000166
AC:
2

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Nov 13, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.091
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.055
DANN
Benign
0.91
DEOGEN2
Benign
0.027
T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.0018
N
LIST_S2
Benign
0.45
T
M_CAP
Benign
0.0030
T
MetaRNN
Benign
0.025
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-0.90
N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
1.6
N
REVEL
Benign
0.026
Sift
Benign
0.35
T
Sift4G
Benign
0.55
T
Polyphen
0.0
B
Vest4
0.072
MutPred
0.26
Loss of methylation at R192 (P = 0.0248);
MVP
0.17
MPC
0.73
ClinPred
0.057
T
GERP RS
-5.3
Varity_R
0.026
gMVP
0.028

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs766887441; hg19: chr19-2252749; COSMIC: COSV55553918; COSMIC: COSV55553918; API