chr7-94552377-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_022900.5(CASD1):āc.1984A>Gā(p.Lys662Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,920 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000034 ( 0 hom. )
Consequence
CASD1
NM_022900.5 missense
NM_022900.5 missense
Scores
3
7
9
Clinical Significance
Conservation
PhyloP100: 9.32
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASD1 | NM_022900.5 | c.1984A>G | p.Lys662Glu | missense_variant | 16/18 | ENST00000297273.9 | |
LOC105375404 | XR_007060433.1 | n.74+6045T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASD1 | ENST00000297273.9 | c.1984A>G | p.Lys662Glu | missense_variant | 16/18 | 1 | NM_022900.5 | P1 | |
CASD1 | ENST00000471944.5 | n.645A>G | non_coding_transcript_exon_variant | 1/3 | 2 | ||||
SGCE | ENST00000645624.1 | n.834-28104T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248222Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 134226
GnomAD3 exomes
AF:
AC:
4
AN:
248222
Hom.:
AF XY:
AC XY:
3
AN XY:
134226
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1458920Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 725700
GnomAD4 exome
AF:
AC:
5
AN:
1458920
Hom.:
Cov.:
30
AF XY:
AC XY:
3
AN XY:
725700
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ExAC
AF:
AC:
2
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 07, 2024 | The c.1984A>G (p.K662E) alteration is located in exon 16 (coding exon 16) of the CASD1 gene. This alteration results from a A to G substitution at nucleotide position 1984, causing the lysine (K) at amino acid position 662 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Loss of methylation at K662 (P = 0.0012);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 50
Find out detailed SpliceAI scores and Pangolin per-transcript scores at