chr7-94555592-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_022900.5(CASD1):āc.2228T>Cā(p.Phe743Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 32)
Exomes š: 0.000011 ( 0 hom. )
Consequence
CASD1
NM_022900.5 missense
NM_022900.5 missense
Scores
6
8
5
Clinical Significance
Conservation
PhyloP100: 7.86
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.843
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASD1 | NM_022900.5 | c.2228T>C | p.Phe743Ser | missense_variant | 18/18 | ENST00000297273.9 | |
LOC105375404 | XR_007060433.1 | n.74+2830A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASD1 | ENST00000297273.9 | c.2228T>C | p.Phe743Ser | missense_variant | 18/18 | 1 | NM_022900.5 | P1 | |
CASD1 | ENST00000471944.5 | n.889T>C | non_coding_transcript_exon_variant | 3/3 | 2 | ||||
CASD1 | ENST00000489196.1 | n.825T>C | non_coding_transcript_exon_variant | 2/2 | 3 | ||||
SGCE | ENST00000645624.1 | n.834-31319A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152040Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250948Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135600
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461426Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727010
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152040Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74260
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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 | Dec 28, 2023 | The c.2228T>C (p.F743S) alteration is located in exon 18 (coding exon 18) of the CASD1 gene. This alteration results from a T to C substitution at nucleotide position 2228, causing the phenylalanine (F) at amino acid position 743 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at