rs17166384

Variant names:

• chr7-94623400-A-G
• rs17166384
• NM_003919.3:c.391-3T>C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_003919.3(SGCE):​c.391-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,582,944 control chromosomes in the GnomAD database, including 2,719 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.076 (1498 hom., cov: 32)
  • Exomes 𝑓: 0.0078 (1221 hom.)
• Consequence: SGCE NM_003919.3 splice_region, intron
• Scores: Splicing: ADA: 0.0004597
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 2.03
• Publications: 6 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 7-94623400-A-G is Benign according to our data. Variant chr7-94623400-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 197225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

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.391-3T>C		splice_region intron	N/A	NP_003910.1	A0A0S2Z4P5
	SGCE	NM_001346713.2		c.499-3T>C		splice_region intron	N/A	NP_001333642.1	A0A2R8YGQ3
	SGCE	NM_001346715.2		c.499-3T>C		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.391-3T>C		splice_region intron	N/A	ENSP00000497130.1	O43556-1
	SGCE	ENST00000428696.7	TSL:1	c.391-3T>C		splice_region intron	N/A	ENSP00000397536.3	A0A2U3TZN7
	SGCE	ENST00000447873.6	TSL:1	c.391-3T>C		splice_region intron	N/A	ENSP00000388734.1	C9JR67

Frequencies

GnomAD3 genomes AF: 0.0758 AC: 11531 AN: 152078 Hom.: 1495 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0284

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.0516

GnomAD2 exomes AF: 0.0200 AC: 4940 AN: 246722 AF XY: 0.0146

Gnomad AFR exome AF: 0.270

Gnomad AMR exome AF: 0.0139

Gnomad ASJ exome AF: 0.00120

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00118

Gnomad OTH exome AF: 0.00849

GnomAD4 exome AF: 0.00781 AC: 11178 AN: 1430748 Hom.: 1221 Cov.: 24 AF XY: 0.00675 AC XY: 4814 AN XY: 713342

African (AFR) AF: 0.265 AC: 8590 AN: 32460

American (AMR) AF: 0.0154 AC: 683 AN: 44384

Ashkenazi Jewish (ASJ) AF: 0.00139 AC: 36 AN: 25890

East Asian (EAS) AF: 0.00 AC: 0 AN: 39340

South Asian (SAS) AF: 0.000401 AC: 34 AN: 84770

European-Finnish (FIN) AF: 0.0000563 AC: 3 AN: 53280

Middle Eastern (MID) AF: 0.0142 AC: 80 AN: 5632

European-Non Finnish (NFE) AF: 0.000747 AC: 811 AN: 1085716

Other (OTH) AF: 0.0159 AC: 941 AN: 59276

GnomAD4 genome AF: 0.0759 AC: 11557 AN: 152196 Hom.: 1498 Cov.: 32 AF XY: 0.0730 AC XY: 5430 AN XY: 74410

African (AFR) AF: 0.263 AC: 10901 AN: 41488

American (AMR) AF: 0.0283 AC: 433 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00141 AC: 96 AN: 68004

Other (OTH) AF: 0.0515 AC: 109 AN: 2116

Alfa AF: 0.0438 Hom.: 1113

Bravo AF: 0.0856

Asia WGS AF: 0.0120 AC: 41 AN: 3454

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Myoclonic dystonia 11 (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	12
DANN	Benign	0.96
PhyloP100		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=76/24	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00046
dbscSNV1_RF	Benign	0.010
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: rs17166384; hg19: chr7-94252712;