7-88210033-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003130.4(SRI):​c.347G>A​(p.Arg116Lys) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SRI
NM_003130.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71
Variant links:
Genes affected
SRI (HGNC:11292): (sorcin) This gene encodes a calcium-binding protein with multiple E-F hand domains that relocates from the cytoplasm to the sarcoplasmic reticulum in response to elevated calcium levels. In addition to regulating intracellular calcium homeostasis it also modulates excitation-contraction coupling in the heart. Alternative splicing results in multiple transcript variants encoding distinct proteins. Multiple pseudogenes exist for this gene. [provided by RefSeq, Mar 2012]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3512398).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SRINM_003130.4 linkc.347G>A p.Arg116Lys missense_variant Exon 5 of 8 ENST00000265729.7 NP_003121.1 P30626-1B4DHQ6
SRINM_001256891.2 linkc.347G>A p.Arg116Lys missense_variant Exon 5 of 7 NP_001243820.1 P30626
SRINM_198901.2 linkc.302G>A p.Arg101Lys missense_variant Exon 5 of 8 NP_944490.1 P30626-2
SRINM_001256892.2 linkc.302G>A p.Arg101Lys missense_variant Exon 5 of 7 NP_001243821.1 P30626-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SRIENST00000265729.7 linkc.347G>A p.Arg116Lys missense_variant Exon 5 of 8 1 NM_003130.4 ENSP00000265729.3 P30626-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.347G>A (p.R116K) alteration is located in exon 5 (coding exon 5) of the SRI gene. This alteration results from a G to A substitution at nucleotide position 347, causing the arginine (R) at amino acid position 116 to be replaced by a lysine (K). 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
0.21
BayesDel_addAF
Benign
-0.0035
T
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.085
T;T;.;.
Eigen
Benign
-0.020
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.61
T;T;T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.35
T;T;T;T
MetaSVM
Benign
-0.58
T
MutationAssessor
Benign
1.7
L;.;.;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-2.1
N;N;N;N
REVEL
Benign
0.20
Sift
Benign
0.057
T;T;T;T
Sift4G
Benign
0.18
T;T;T;T
Polyphen
0.15
B;B;.;.
Vest4
0.34
MutPred
0.36
Gain of ubiquitination at R116 (P = 0.0155);.;.;.;
MVP
0.88
MPC
0.14
ClinPred
0.45
T
GERP RS
5.9
Varity_R
0.63
gMVP
0.60

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: chr7-87839348; API