rs752074255

Variant names:

• chr7-94623352-A-G
• rs752074255
• NM_003919.3:c.436T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-94623352-A-G
• chr7-94623352-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_003919.3(SGCE):​c.436T>C​(p.Leu146Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000362 in 1,604,200 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000039 (1 hom.)
• Consequence: SGCE NM_003919.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.52
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 7-94623352-A-G is Benign according to our data. Variant chr7-94623352-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 703274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.52 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0000386 (56/1451926) while in subpopulation MID AF = 0.00053 (3/5658). AF 95% confidence interval is 0.000263. There are 1 homozygotes in GnomAdExome4. There are 29 alleles in the male GnomAdExome4 subpopulation. Median coverage is 27. This position passed quality control check.
• BS2: High AC in GnomAdExome4 at 56 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.436T>C	p.Leu146Leu	synonymous	Exon 4 of 11	NP_003910.1	A0A0S2Z4P5
	SGCE	NM_001346713.2		c.544T>C	p.Leu182Leu	synonymous	Exon 5 of 12	NP_001333642.1	A0A2R8YGQ3
	SGCE	NM_001346715.2		c.544T>C	p.Leu182Leu	synonymous	Exon 5 of 11	NP_001333644.1	A0A2R8Y5J3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCE	ENST00000648936.2	MANE Select	c.436T>C	p.Leu146Leu	synonymous	Exon 4 of 11	ENSP00000497130.1	O43556-1
	SGCE	ENST00000428696.7	TSL:1	c.436T>C	p.Leu146Leu	synonymous	Exon 4 of 11	ENSP00000397536.3	A0A2U3TZN7
	SGCE	ENST00000447873.6	TSL:1	c.436T>C	p.Leu146Leu	synonymous	Exon 4 of 10	ENSP00000388734.1	C9JR67

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000723 AC: 18 AN: 248880 AF XY: 0.0000743

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000585

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000621

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000386 AC: 56 AN: 1451926 Hom.: 1 Cov.: 27 AF XY: 0.0000401 AC XY: 29 AN XY: 722676

African (AFR) AF: 0.00 AC: 0 AN: 33246

American (AMR) AF: 0.0000674 AC: 3 AN: 44478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26002

East Asian (EAS) AF: 0.00 AC: 0 AN: 39472

South Asian (SAS) AF: 0.000363 AC: 31 AN: 85332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53280

Middle Eastern (MID) AF: 0.000530 AC: 3 AN: 5658

European-Non Finnish (NFE) AF: 0.0000145 AC: 16 AN: 1104422

Other (OTH) AF: 0.0000500 AC: 3 AN: 60036

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74464

African (AFR) AF: 0.00 AC: 0 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Myoclonic dystonia 11 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.9
DANN	Benign	0.81
PhyloP100		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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: rs752074255; hg19: chr7-94252664;