7-88210033-C-T

Variant names:

• chr7-88210033-C-T
• NM_003130.4:c.347G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71

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]

ACMG classification

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
SRI	NM_003130.4	c.347G>A	p.Arg116Lys	missense_variant	Exon 5 of 8	ENST00000265729.7	NP_003121.1
SRI	NM_001256891.2	c.347G>A	p.Arg116Lys	missense_variant	Exon 5 of 7		NP_001243820.1
SRI	NM_198901.2	c.302G>A	p.Arg101Lys	missense_variant	Exon 5 of 8		NP_944490.1
SRI	NM_001256892.2	c.302G>A	p.Arg101Lys	missense_variant	Exon 5 of 7		NP_001243821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRI	ENST00000265729.7	c.347G>A	p.Arg116Lys	missense_variant	Exon 5 of 8	1	NM_003130.4	ENSP00000265729.3

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

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;