NM_003919.3:c.369G>C

Variant names:

• chr7-94628223-C-G
• rs140913016
• NM_003919.3:c.369G>C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_003919.3(SGCE):​c.369G>C​(p.Val123Val) variant causes a synonymous change. The variant allele was found at a frequency of 0.000604 in 1,611,698 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (2 hom.)
• Consequence: SGCE NM_003919.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 4.45
• 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 7-94628223-C-G is Benign according to our data. Variant chr7-94628223-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259197.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 = 0.0035 (532/151844) while in subpopulation AFR AF = 0.0122 (506/41460). AF 95% confidence interval is 0.0113. There are 3 homozygotes in GnomAd4. There are 247 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 532 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.369G>C	p.Val123Val	synonymous	Exon 3 of 11	NP_003910.1	A0A0S2Z4P5
	SGCE	NM_001346713.2		c.477G>C	p.Val159Val	synonymous	Exon 4 of 12	NP_001333642.1	A0A2R8YGQ3
	SGCE	NM_001346715.2		c.477G>C	p.Val159Val	synonymous	Exon 4 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.369G>C	p.Val123Val	synonymous	Exon 3 of 11	ENSP00000497130.1	O43556-1
	SGCE	ENST00000428696.7	TSL:1	c.369G>C	p.Val123Val	synonymous	Exon 3 of 11	ENSP00000397536.3	A0A2U3TZN7
	SGCE	ENST00000447873.6	TSL:1	c.369G>C	p.Val123Val	synonymous	Exon 3 of 10	ENSP00000388734.1	C9JR67

Frequencies

GnomAD3 genomes AF: 0.00353 AC: 535 AN: 151726 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000937 AC: 234 AN: 249692 AF XY: 0.000726

Gnomad AFR exome AF: 0.0129

Gnomad AMR exome AF: 0.000670

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.000303 AC: 442 AN: 1459854 Hom.: 2 Cov.: 30 AF XY: 0.000252 AC XY: 183 AN XY: 726194

African (AFR) AF: 0.0111 AC: 372 AN: 33418

American (AMR) AF: 0.000673 AC: 30 AN: 44544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26062

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.00 AC: 0 AN: 86148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110778

Other (OTH) AF: 0.000647 AC: 39 AN: 60278

GnomAD4 genome AF: 0.00350 AC: 532 AN: 151844 Hom.: 3 Cov.: 32 AF XY: 0.00333 AC XY: 247 AN XY: 74234

African (AFR) AF: 0.0122 AC: 506 AN: 41460

American (AMR) AF: 0.00132 AC: 20 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67822

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.000917 Hom.: 0

Bravo AF: 0.00406

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	9.2
DANN	Benign	0.80
PhyloP100		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=89/11	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: rs140913016; hg19: chr7-94257535; COSMIC: COSV99722341; COSMIC: COSV99722341;