chr19-2255312-C-G

Position:

• chr19-2255312-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 8P and 8B. PVS1 BA1

The NM_144616.4(JSRP1):​c.3G>C​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0569 in 1,605,768 control chromosomes in the GnomAD database, including 9,892 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (4189 hom., cov: 32)
  • Exomes 𝑓: 0.047 (5703 hom.)
• Consequence: JSRP1 NM_144616.4 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JSRP1	NM_144616.4	c.3G>C	p.Met1?	start_lost	2/7	ENST00000300961.10	NP_653217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JSRP1	ENST00000300961.10	c.3G>C	p.Met1?	start_lost	2/7	2	NM_144616.4	ENSP00000300961.4
JSRP1	ENST00000593238.2	n.459G>C		non_coding_transcript_exon_variant	2/5	5

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23626 AN: 152060 Hom.: 4183 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.00773

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0227

Gnomad OTH AF: 0.129

GnomAD3 exomes AF: 0.0883 AC: 21554 AN: 244088 Hom.: 2461 AF XY: 0.0805 AC XY: 10724 AN XY: 133180

Gnomad AFR exome AF: 0.424

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.0341

Gnomad EAS exome AF: 0.244

Gnomad SAS exome AF: 0.115

Gnomad FIN exome AF: 0.00607

Gnomad NFE exome AF: 0.0233

Gnomad OTH exome AF: 0.0596

GnomAD4 exome AF: 0.0466 AC: 67725 AN: 1453590 Hom.: 5703 Cov.: 30 AF XY: 0.0468 AC XY: 33839 AN XY: 723100

Gnomad4 AFR exome AF: 0.431

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.0349

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.00675

Gnomad4 NFE exome AF: 0.0219

Gnomad4 OTH exome AF: 0.0712

GnomAD4 genome AF: 0.156 AC: 23674 AN: 152178 Hom.: 4189 Cov.: 32 AF XY: 0.155 AC XY: 11561 AN XY: 74418

Gnomad4 AFR AF: 0.420

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.00773

Gnomad4 NFE AF: 0.0227

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0562 Hom.: 345

Bravo AF: 0.176

TwinsUK AF: 0.0181 AC: 67

ALSPAC AF: 0.0218 AC: 84

ESP6500AA AF: 0.413 AC: 1817

ESP6500EA AF: 0.0243 AC: 209

ExAC AF: 0.0909 AC: 10997

Asia WGS AF: 0.227 AC: 787 AN: 3478

EpiCase AF: 0.0260

EpiControl AF: 0.0243

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.54
DANN	Benign	0.64
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0010	T
MetaSVM	Benign	-0.92	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.091
Sift	Benign	1.0	T
Sift4G	Benign	0.86	T
Polyphen		0.0	B
Vest4		0.019
MutPred		0.49		Loss of disorder (P = 0.0385);
ClinPred		0.0016	T
GERP RS		1.7
Varity_R		0.063
gMVP		0.062

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

Other links and lift over

dbSNP: rs7250822; hg19: chr19-2255311; COSMIC: COSV55558698; COSMIC: COSV55558698;