dbSNP rs1063964: SRI:c.*324C>T (chr7-88206154-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.350

Publications

36 publications found

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]

SRI Gene-Disease associations (from GenCC):

hypertrophic cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

SRI links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRI	NM_003130.4 link	c.*324C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000265729.7	NP_003121.1	P30626-1B4DHQ6
SRI	NM_198901.2 link	c.*324C>T		3_prime_UTR_variant	Exon 8 of 8		NP_944490.1	P30626-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SRI	ENST00000265729.7 link	c.*324C>T	3_prime_UTR_variant	Exon 8 of 8	1	NM_003130.4	ENSP00000265729.3	P30626-1
SRI	ENST00000419179.5 link	c.*324C>T	3_prime_UTR_variant	Exon 8 of 8	2		ENSP00000397609.1	B4DHQ6
SRI	ENST00000472930.6 link	n.*132C>T	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.333

AC:

50474

AN:

151774

Hom.:

9296

Cov.:

show subpopulations

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.:

AF XY:

0.251

AC XY:

27834

AN XY:

110692

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1839

3678

5518

7357

9196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

202

404

606

808

1010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.333

AC:

50517

AN:

151892

Hom.:

9305

Cov.:

AF XY:

0.326

AC XY:

24179

AN XY:

74238

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.316

AC:

21460

AN:

67918

Other (OTH)

AF:

0.281

AC:

592

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1630

3260

4889

6519

8149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

476

952

1428

1904

2380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.8

(source)

DANN

Benign

0.47

PhyloP100

0.35

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over