NM_022900.5:c.1162A>C

Variant summary

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

The NM_022900.5(CASD1):​c.1162A>C​(p.Asn388His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,800 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N388D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CASD1
NM_022900.5 missense

Scores

10
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.33

Publications

0 publications found
Variant links:
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), Illumina
  • myoclonus-dystonia syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

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;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CASD1NM_022900.5 linkc.1162A>C p.Asn388His missense_variant Exon 9 of 18 ENST00000297273.9 NP_075051.4 Q96PB1Q8WZ77

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CASD1ENST00000297273.9 linkc.1162A>C p.Asn388His missense_variant Exon 9 of 18 1 NM_022900.5 ENSP00000297273.4 Q96PB1
SGCEENST00000645624.1 linkn.834-13517T>G intron_variant Intron 6 of 6
ENSG00000309657ENST00000842810.1 linkn.150+20691T>G intron_variant Intron 2 of 3
ENSG00000309657ENST00000842811.1 linkn.172+20632T>G intron_variant Intron 2 of 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000399
AC:
1
AN:
250612
AF XY:
0.00000738
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460800
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726750
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33448
American (AMR)
AF:
0.00
AC:
0
AN:
44712
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26118
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39656
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86220
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53264
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
9.00e-7
AC:
1
AN:
1111256
Other (OTH)
AF:
0.00
AC:
0
AN:
60362
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
15
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.47
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.055
T
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.97
D
M_CAP
Benign
0.015
T
MetaRNN
Uncertain
0.56
D
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.75
N
PhyloP100
3.3
PrimateAI
Uncertain
0.54
T
PROVEAN
Uncertain
-2.8
D
REVEL
Benign
0.24
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.011
D
Polyphen
0.98
D
Vest4
0.47
MutPred
0.75
Gain of disorder (P = 0.0824);
MVP
0.52
MPC
1.2
ClinPred
0.83
D
GERP RS
2.9
Varity_R
0.40
gMVP
0.59
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

Publications

Other links and lift over

dbSNP: rs116301340; hg19: chr7-94167102; API