19-2252522-C-T

Position:

• chr19-2252522-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144616.4(JSRP1):​c.803G>A​(p.Arg268Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: JSRP1 NM_144616.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.489

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]

ACMG classification

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=0.07167238).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JSRP1	NM_144616.4	c.803G>A	p.Arg268Gln	missense_variant	7/7	ENST00000300961.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JSRP1	ENST00000300961.10	c.803G>A	p.Arg268Gln	missense_variant	7/7	2	NM_144616.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2024

The c.803G>A (p.R268Q) alteration is located in exon 7 (coding exon 6) of the JSRP1 gene. This alteration results from a G to A substitution at nucleotide position 803, causing the arginine (R) at amino acid position 268 to be replaced by a glutamine (Q). 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	Benign	0.14
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.26	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.024
Sift	Benign	0.55	T
Sift4G	Benign	0.61	T
Polyphen		0.65	P
Vest4		0.089
MutPred		0.21		Loss of MoRF binding (P = 0.0397);
MVP		0.33
MPC		1.5
ClinPred		0.21	T
GERP RS		1.5
Varity_R		0.024
gMVP		0.022

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-2252521;