7-88206154-G-A

Variant names:

• chr7-88206154-G-A
• rs1063964
• NM_003130.4:c.*324C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003130.4(SRI):​c.*324C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 359,442 control chromosomes in the GnomAD database, including 18,099 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 0.33 (9305 hom., cov: 32)
  • Exomes 𝑓: 0.27 (8794 hom.)
• Consequence: SRI NM_003130.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.350
• Publications: 36 publications found

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]

SRI Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003130.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRI	NM_003130.4	MANE Select	c.*324C>T		3_prime_UTR	Exon 8 of 8	NP_003121.1
	SRI	NM_198901.2		c.*324C>T		3_prime_UTR	Exon 8 of 8	NP_944490.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRI	ENST00000265729.7	TSL:1 MANE Select	c.*324C>T		3_prime_UTR	Exon 8 of 8	ENSP00000265729.3
	SRI	ENST00000419179.5	TSL:2	c.*324C>T		3_prime_UTR	Exon 8 of 8	ENSP00000397609.1
	SRI	ENST00000472930.6	TSL:2	n.*132C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50474 AN: 151774 Hom.: 9296 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.0638

Gnomad SAS AF: 0.0870

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.267 AC: 55490 AN: 207550 Hom.: 8794 Cov.: 0 AF XY: 0.251 AC XY: 27834 AN XY: 110692

African (AFR) AF: 0.473 AC: 3278 AN: 6926

American (AMR) AF: 0.184 AC: 1821 AN: 9876

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 1380 AN: 5902

East Asian (EAS) AF: 0.0663 AC: 837 AN: 12620

South Asian (SAS) AF: 0.0912 AC: 2544 AN: 27910

European-Finnish (FIN) AF: 0.355 AC: 3233 AN: 9098

Middle Eastern (MID) AF: 0.230 AC: 188 AN: 816

European-Non Finnish (NFE) AF: 0.317 AC: 39032 AN: 122936

Other (OTH) AF: 0.277 AC: 3177 AN: 11466

GnomAD4 genome AF: 0.333 AC: 50517 AN: 151892 Hom.: 9305 Cov.: 32 AF XY: 0.326 AC XY: 24179 AN XY: 74238

African (AFR) AF: 0.466 AC: 19310 AN: 41400

American (AMR) AF: 0.225 AC: 3434 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 778 AN: 3466

East Asian (EAS) AF: 0.0638 AC: 330 AN: 5174

South Asian (SAS) AF: 0.0869 AC: 419 AN: 4824

European-Finnish (FIN) AF: 0.357 AC: 3757 AN: 10522

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21460 AN: 67918

Other (OTH) AF: 0.281 AC: 592 AN: 2108

Alfa AF: 0.309 Hom.: 14677

Bravo AF: 0.329

Asia WGS AF: 0.0980 AC: 344 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.47
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

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: rs1063964; hg19: chr7-87835469;