chr7-94554522-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_022900.5(CASD1):c.2074G>A(p.Ala692Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000508 in 1,612,024 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00053 ( 1 hom. )
Consequence
CASD1
NM_022900.5 missense
NM_022900.5 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 5.55
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 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33909816).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASD1 | NM_022900.5 | c.2074G>A | p.Ala692Thr | missense_variant | 17/18 | ENST00000297273.9 | |
LOC105375404 | XR_007060433.1 | n.74+3900C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASD1 | ENST00000297273.9 | c.2074G>A | p.Ala692Thr | missense_variant | 17/18 | 1 | NM_022900.5 | P1 | |
CASD1 | ENST00000471944.5 | n.735G>A | non_coding_transcript_exon_variant | 2/3 | 2 | ||||
CASD1 | ENST00000489196.1 | n.671G>A | non_coding_transcript_exon_variant | 1/2 | 3 | ||||
SGCE | ENST00000645624.1 | n.834-30249C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000276 AC: 42AN: 152054Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
42
AN:
152054
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000215 AC: 54AN: 250628Hom.: 0 AF XY: 0.000192 AC XY: 26AN XY: 135460
GnomAD3 exomes
AF:
AC:
54
AN:
250628
Hom.:
AF XY:
AC XY:
26
AN XY:
135460
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: 0.000532 AC: 777AN: 1459970Hom.: 1 Cov.: 29 AF XY: 0.000511 AC XY: 371AN XY: 726308
GnomAD4 exome
AF:
AC:
777
AN:
1459970
Hom.:
Cov.:
29
AF XY:
AC XY:
371
AN XY:
726308
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 AF: 0.000276 AC: 42AN: 152054Hom.: 0 Cov.: 32 AF XY: 0.000323 AC XY: 24AN XY: 74248
GnomAD4 genome
AF:
AC:
42
AN:
152054
Hom.:
Cov.:
32
AF XY:
AC XY:
24
AN XY:
74248
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
2
ALSPAC
AF:
AC:
0
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
4
ExAC
AF:
AC:
28
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 | May 30, 2024 | The c.2074G>A (p.A692T) alteration is located in exon 17 (coding exon 17) of the CASD1 gene. This alteration results from a G to A substitution at nucleotide position 2074, causing the alanine (A) at amino acid position 692 to be replaced by a threonine (T). 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at