Genetic Variant SGCE:p.Pro399Arg (chr7-94598832-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003919.3(SGCE):c.1196C>G(p.Pro399Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P399L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

SGCE
NM_003919.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.58

Publications

0 publications found

Variant links:

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]

SGCE links:

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]

CASD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SGCE	NM_003919.3	MANE Select	c.1196C>G	p.Pro399Arg	missense	Exon 9 of 11	NP_003910.1	A0A0S2Z4P5
SGCE	NM_001346713.2		c.1304C>G	p.Pro435Arg	missense	Exon 10 of 12	NP_001333642.1	A0A2R8YGQ3
SGCE	NM_001346715.2		c.1277C>G	p.Pro426Arg	missense	Exon 9 of 11	NP_001333644.1	A0A2R8Y5J3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SGCE	ENST00000648936.2	MANE Select	c.1196C>G	p.Pro399Arg	missense	Exon 9 of 11	ENSP00000497130.1	O43556-1
SGCE	ENST00000428696.7	TSL:1	c.1148C>G	p.Pro383Arg	missense	Exon 8 of 11	ENSP00000397536.3	A0A2U3TZN7
SGCE	ENST00000447873.6	TSL:1	c.1169C>G	p.Pro390Arg	missense	Exon 8 of 10	ENSP00000388734.1	C9JR67

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Myoclonic dystonia 11 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.75

Eigen

Benign

0.077

Eigen_PC

Benign

0.11

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.22

MetaRNN

Uncertain

0.68

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.3

PhyloP100

7.6

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.2

REVEL

Pathogenic

0.65

Sift

Benign

0.032

Sift4G

Pathogenic

0.0

Polyphen

0.0030

Vest4

0.64

MutPred

0.62

Loss of glycosylation at T439 (P = 0.0778)

MVP

0.81

MPC

0.22

ClinPred

0.97

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.43

gMVP

0.66

Mutation Taster

=57/43

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over