chr7-94537559-C-T

Variant names:

• chr7-94537559-C-T
• NM_022900.5:c.931C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022900.5(CASD1):​c.931C>T​(p.Leu311Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CASD1 NM_022900.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73
• Publications: 0 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• myoclonic dystonia 11

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia, Illumina
• myoclonus-dystonia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000309657 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14547473).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022900.5. 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
	CASD1	NM_022900.5	MANE Select	c.931C>T	p.Leu311Phe	missense	Exon 9 of 18	NP_075051.4
	CASD1	NM_001363426.1		c.502C>T	p.Leu168Phe	missense	Exon 10 of 19	NP_001350355.1
	CASD1	NM_001363428.1		c.376C>T	p.Leu126Phe	missense	Exon 9 of 18	NP_001350357.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASD1	ENST00000297273.9	TSL:1 MANE Select	c.931C>T	p.Leu311Phe	missense	Exon 9 of 18	ENSP00000297273.4	Q96PB1
	CASD1	ENST00000919855.1		c.931C>T	p.Leu311Phe	missense	Exon 9 of 18	ENSP00000589914.1
	CASD1	ENST00000919856.1		c.886C>T	p.Leu296Phe	missense	Exon 8 of 17	ENSP00000589915.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.070
Eigen_PC	Benign	0.040
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.7
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.029
Sift	Benign	0.11	T
Sift4G	Benign	0.62	T
Polyphen		0.45	P
Vest4		0.38
MutPred		0.35		Gain of catalytic residue at L311 (P = 0.0998)
MVP		0.40
MPC		0.93
ClinPred		0.49	T
GERP RS		4.1
Varity_R		0.069
gMVP		0.38
Mutation Taster		=82/18	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

hg19: chr7-94166871;