Genetic Variant NM_144616.4:c.400G>C (chr19-2253656-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144616.4(JSRP1):c.400G>C(p.Val134Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V134M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

JSRP1
NM_144616.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.390

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09668499).

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.400G>C	p.Val134Leu	missense	Exon 5 of 7	NP_653217.1	Q96MG2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JSRP1	ENST00000300961.10	TSL:2 MANE Select	c.400G>C	p.Val134Leu	missense	Exon 5 of 7	ENSP00000300961.4	Q96MG2
JSRP1	ENST00000862809.1		c.400G>C	p.Val134Leu	missense	Exon 5 of 7	ENSP00000532868.1
JSRP1	ENST00000967628.1		c.421G>C	p.Val141Leu	missense	Exon 5 of 7	ENSP00000637687.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

103884

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1355108

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

668920

African (AFR)

AF:

0.00

AC:

AN:

27716

American (AMR)

AF:

0.00

AC:

AN:

32406

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24096

East Asian (EAS)

AF:

0.00

AC:

AN:

31626

South Asian (SAS)

AF:

0.00

AC:

AN:

76272

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34772

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5010

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1066796

Other (OTH)

AF:

0.00

AC:

AN:

56414

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.15

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.57

M_CAP

Benign

0.021

MetaRNN

Benign

0.097

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-0.39

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.4

REVEL

Benign

0.042

Sift

Benign

0.17

Sift4G

Benign

0.26

Polyphen

0.11

Vest4

0.26

MutPred

0.34

Loss of catalytic residue at V134 (P = 0.0396)

MVP

0.33

MPC

0.12

ClinPred

0.25

GERP RS

-1.7

Varity_R

0.12

gMVP

0.081

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over