Variant chr19-2253697-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.359G>A(p.Gly120Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000739 in 1,353,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000074 ( 0 hom. )

Consequence

JSRP1
NM_144616.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.190

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:

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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=0.07406348).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JSRP1	NM_144616.4 linkuse as main transcript	c.359G>A	p.Gly120Glu	missense_variant	5/7	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.359G>A	p.Gly120Glu	missense_variant	5/7	2	NM_144616.4	ENSP00000300961.4		Q96MG2
JSRP1	ENST00000593238.2 linkuse as main transcript	n.815G>A		non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000385

AC:

AN:

103798

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

58108

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:

0.000205

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000739

AC:

AN:

1353980

Hom.:

Cov.:

AF XY:

0.00000898

AC XY:

AN XY:

668078

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000263

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000656

Gnomad4 OTH exome

AF:

0.0000177

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

May 24, 2023

The c.359G>A (p.G120E) alteration is located in exon 5 (coding exon 4) of the JSRP1 gene. This alteration results from a G to A substitution at nucleotide position 359, causing the glycine (G) at amino acid position 120 to be replaced by a glutamic acid (E). 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

0.37

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.092

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.61

M_CAP

Benign

0.013

MetaRNN

Benign

0.074

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.98

N;N

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.027

Polyphen

0.0030

Vest4

0.14

MutPred

0.22

Loss of catalytic residue at G120 (P = 0.0296);

MVP

0.34

MPC

0.033

ClinPred

0.21

GERP RS

2.7

Varity_R

0.42

gMVP

0.032

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.

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