rs201696689

Variant names:

• chr7-94588738-AATG-A
• rs201696689
• NM_003919.3:c.1254-9_1254-7delCAT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_003919.3(SGCE):​c.1254-9_1254-7delCAT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000449 in 1,613,304 control chromosomes in the GnomAD database, including 4 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (2 hom.)
• Consequence: SGCE NM_003919.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 3.05
• Publications: 0 publications found

Genes affected

SGCE (HGNC:10808): (sarcoglycan epsilon) This gene encodes the epsilon member of the sarcoglycan family. Sarcoglycans are transmembrane proteins that are components of the dystrophin-glycoprotein complex, which link the actin cytoskeleton to the extracellular matrix. Unlike other family members which are predominantly expressed in striated muscle, the epsilon sarcoglycan is more broadly expressed. Mutations in this gene are associated with myoclonus-dystonia syndrome. This gene is imprinted, with preferential expression from the paternal allele. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. A pseudogene associated with this gene is located on chromosome 2. [provided by RefSeq, Oct 2016]

CASD1 (HGNC:16014): (CAS1 domain containing 1) Enables N-acetylneuraminate 7-O(or 9-O)-acetyltransferase activity. Involved in carbohydrate metabolic process. Is integral component of Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 7-94588738-AATG-A is Benign according to our data. Variant chr7-94588738-AATG-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 448355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00225 (342/152244) while in subpopulation AFR AF = 0.00748 (311/41560). AF 95% confidence interval is 0.0068. There are 2 homozygotes in GnomAd4. There are 159 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 342 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003919.3. 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
	SGCE	NM_003919.3	MANE Select	c.1254-9_1254-7delCAT		splice_region intron	N/A	NP_003910.1	A0A0S2Z4P5
	SGCE	NM_001346713.2		c.1362-9_1362-7delCAT		splice_region intron	N/A	NP_001333642.1	A0A2R8YGQ3
	SGCE	NM_001346715.2		c.1335-9_1335-7delCAT		splice_region intron	N/A	NP_001333644.1	A0A2R8Y5J3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCE	ENST00000648936.2	MANE Select	c.1254-9_1254-7delCAT		splice_region intron	N/A	ENSP00000497130.1	O43556-1
	SGCE	ENST00000428696.7	TSL:1	c.1206-9_1206-7delCAT		splice_region intron	N/A	ENSP00000397536.3	A0A2U3TZN7
	SGCE	ENST00000447873.6	TSL:1	c.1227-9_1227-7delCAT		splice_region intron	N/A	ENSP00000388734.1	C9JR67

Frequencies

GnomAD3 genomes AF: 0.00222 AC: 338 AN: 152126 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00741

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000618 AC: 155 AN: 250850 AF XY: 0.000487

Gnomad AFR exome AF: 0.00781

Gnomad AMR exome AF: 0.000550

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.000654

GnomAD4 exome AF: 0.000261 AC: 382 AN: 1461060 Hom.: 2 AF XY: 0.000227 AC XY: 165 AN XY: 726876

African (AFR) AF: 0.00813 AC: 272 AN: 33452

American (AMR) AF: 0.000537 AC: 24 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5758

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1111390

Other (OTH) AF: 0.000894 AC: 54 AN: 60374

GnomAD4 genome AF: 0.00225 AC: 342 AN: 152244 Hom.: 2 Cov.: 32 AF XY: 0.00214 AC XY: 159 AN XY: 74430

African (AFR) AF: 0.00748 AC: 311 AN: 41560

American (AMR) AF: 0.00118 AC: 18 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68004

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00139 Hom.: 0

Bravo AF: 0.00236

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Myoclonic dystonia 11 (1)
-	-	1	not specified (1)
-	-	1	SGCE-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs201696689; hg19: chr7-94218050;