7-88220357-CTTTT-CT

Variant names:

• chr7-88220357-CTTT-C
• rs60686940
• NM_198901.2:c.7-1418_7-1416delAAA

Variant summary

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

The NM_198901.2(SRI):​c.7-1418_7-1416delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00071 (0 hom., cov: 0)
• Consequence: SRI NM_198901.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245
• Publications: 0 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-AS1 (HGNC:40564): (SRI antisense RNA 1)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198901.2. 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
	SRI	NM_198901.2		c.7-1418_7-1416delAAA		intron	N/A	NP_944490.1	P30626-2
	SRI	NM_001256892.2		c.7-1418_7-1416delAAA		intron	N/A	NP_001243821.1	P30626-3
	SRI-AS1	NR_120517.1		n.574+1146_574+1148delTTT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRI	ENST00000394641.7	TSL:2	c.7-1418_7-1416delAAA		intron	N/A	ENSP00000378137.3	P30626-2
	SRI	ENST00000431660.5	TSL:2	c.7-1418_7-1416delAAA		intron	N/A	ENSP00000391148.1	P30626-3
	SRI	ENST00000490437.5	TSL:2	c.7-3169_7-3167delAAA		intron	N/A	ENSP00000418512.1	C9J0K6

Frequencies

GnomAD3 genomes AF: 0.000700 AC: 103 AN: 147248 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000199

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000405

Gnomad ASJ AF: 0.00116

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00418

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000672

Gnomad OTH AF: 0.000987

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000713 AC: 105 AN: 147302 Hom.: 0 Cov.: 0 AF XY: 0.000727 AC XY: 52 AN XY: 71478

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000249 AC: 10 AN: 40218

American (AMR) AF: 0.000405 AC: 6 AN: 14816

Ashkenazi Jewish (ASJ) AF: 0.00116 AC: 4 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 4950

South Asian (SAS) AF: 0.00 AC: 0 AN: 4652

European-Finnish (FIN) AF: 0.00418 AC: 38 AN: 9096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000673 AC: 45 AN: 66910

Other (OTH) AF: 0.000980 AC: 2 AN: 2040

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 1242

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.24

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs60686940; hg19: chr7-87849672;