rs148979783

Variant names:

• chr7-94618814-T-C
• rs148979783
• NM_003919.3:c.606A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-94618814-T-C
• chr7-94618814-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_003919.3(SGCE):​c.606A>G​(p.Thr202Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,614,112 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T202T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00095 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000077 (1 hom.)
• Consequence: SGCE NM_003919.3 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: -1.26
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 7-94618814-T-C is Benign according to our data. Variant chr7-94618814-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 94383.
• BP7: Synonymous conserved (PhyloP=-1.26 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000945 (144/152344) while in subpopulation AFR AF = 0.00298 (124/41584). AF 95% confidence interval is 0.00255. There are 0 homozygotes in GnomAd4. There are 81 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 144 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.606A>G	p.Thr202Thr	synonymous	Exon 5 of 11	NP_003910.1	A0A0S2Z4P5
	SGCE	NM_001346713.2		c.714A>G	p.Thr238Thr	synonymous	Exon 6 of 12	NP_001333642.1	A0A2R8YGQ3
	SGCE	NM_001346715.2		c.714A>G	p.Thr238Thr	synonymous	Exon 6 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.606A>G	p.Thr202Thr	synonymous	Exon 5 of 11	ENSP00000497130.1	O43556-1
	SGCE	ENST00000428696.7	TSL:1	c.585A>G	p.Thr195Thr	synonymous	Exon 5 of 11	ENSP00000397536.3	A0A2U3TZN7
	SGCE	ENST00000447873.6	TSL:1	c.606A>G	p.Thr202Thr	synonymous	Exon 5 of 10	ENSP00000388734.1	C9JR67

Frequencies

GnomAD3 genomes AF: 0.000946 AC: 144 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00299

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

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: 0.0000294

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000243 AC: 61 AN: 250964 AF XY: 0.000206

Gnomad AFR exome AF: 0.00295

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000773 AC: 113 AN: 1461768 Hom.: 1 Cov.: 31 AF XY: 0.0000591 AC XY: 43 AN XY: 727180

African (AFR) AF: 0.00224 AC: 75 AN: 33474

American (AMR) AF: 0.000335 AC: 15 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111950

Other (OTH) AF: 0.000132 AC: 8 AN: 60386

GnomAD4 genome AF: 0.000945 AC: 144 AN: 152344 Hom.: 0 Cov.: 32 AF XY: 0.00109 AC XY: 81 AN XY: 74506

African (AFR) AF: 0.00298 AC: 124 AN: 41584

American (AMR) AF: 0.000980 AC: 15 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.000664 Hom.: 0

Bravo AF: 0.00106

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.4
DANN	Benign	0.29
PhyloP100		-1.3
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: rs148979783; hg19: chr7-94248126;