19-2252416-C-T

Variant names:

• chr19-2252416-C-T
• rs371559853
• NM_144616.4:c.909G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_144616.4(JSRP1):​c.909G>A​(p.Lys303Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,212 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: JSRP1 NM_144616.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-0.209 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144616.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JSRP1	NM_144616.4	MANE Select	c.909G>A	p.Lys303Lys	synonymous	Exon 7 of 7	NP_653217.1	Q96MG2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JSRP1	ENST00000300961.10	TSL:2 MANE Select	c.909G>A	p.Lys303Lys	synonymous	Exon 7 of 7	ENSP00000300961.4	Q96MG2
	JSRP1	ENST00000862809.1		c.930G>A	p.Lys310Lys	synonymous	Exon 7 of 7	ENSP00000532868.1
	JSRP1	ENST00000967628.1		c.930G>A	p.Lys310Lys	synonymous	Exon 7 of 7	ENSP00000637687.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456212 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 724294

African (AFR) AF: 0.00 AC: 0 AN: 33388

American (AMR) AF: 0.00 AC: 0 AN: 44542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 85964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4488

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111090

Other (OTH) AF: 0.00 AC: 0 AN: 60070

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.1
DANN	Benign	0.90
PhyloP100		-0.21

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

Other links and lift over

dbSNP: rs371559853; hg19: chr19-2252415;