7-94528227-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022900.5(CASD1):​c.436C>T​(p.Gln146*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000687 in 1,455,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CASD1
NM_022900.5 stop_gained

Scores

4
2
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.20
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]

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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 rank MANE Protein UniProt
CASD1NM_022900.5 linkc.436C>T p.Gln146* stop_gained Exon 5 of 18 ENST00000297273.9 NP_075051.4 Q96PB1Q8WZ77

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CASD1ENST00000297273.9 linkc.436C>T p.Gln146* stop_gained Exon 5 of 18 1 NM_022900.5 ENSP00000297273.4 Q96PB1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000403
AC:
1
AN:
248096
Hom.:
0
AF XY:
0.00000746
AC XY:
1
AN XY:
134124
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000887
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1455668
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
724346
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.02e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000595

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.61
D
BayesDel_noAF
Pathogenic
0.63
CADD
Pathogenic
38
DANN
Uncertain
1.0
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.88
FATHMM_MKL
Uncertain
0.96
D
Vest4
0.46
GERP RS
4.8

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.35
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.35
Position offset: 23

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1554408947; hg19: chr7-94157539; API