chr7-94555679-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_022900.5(CASD1):c.2315T>C(p.Leu772Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,280 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
CASD1
NM_022900.5 missense
NM_022900.5 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 4.99
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 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.2315T>C | p.Leu772Ser | missense_variant | 18/18 | ENST00000297273.9 | |
LOC105375404 | XR_007060433.1 | n.74+2743A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASD1 | ENST00000297273.9 | c.2315T>C | p.Leu772Ser | missense_variant | 18/18 | 1 | NM_022900.5 | P1 | |
CASD1 | ENST00000471944.5 | n.976T>C | non_coding_transcript_exon_variant | 3/3 | 2 | ||||
CASD1 | ENST00000489196.1 | n.912T>C | non_coding_transcript_exon_variant | 2/2 | 3 | ||||
SGCE | ENST00000645624.1 | n.834-31406A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152004Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250514Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135356
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461276Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726938
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152004Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74262
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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 | Feb 07, 2023 | The c.2315T>C (p.L772S) 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 2315, causing the leucine (L) at amino acid position 772 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
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
D
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of disorder (P = 0.0063);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
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