chr1-110896653-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000560.4(CD53):c.424C>G(p.Leu142Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,611,898 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
CD53
NM_000560.4 missense, splice_region
NM_000560.4 missense, splice_region
Scores
8
6
Splicing: ADA: 0.001315
2
Clinical Significance
Conservation
PhyloP100: 0.336
Genes affected
CD53 (HGNC:1686): (CD53 molecule) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that is known to complex with integrins. It contributes to the transduction of CD2-generated signals in T cells and natural killer cells and has been suggested to play a role in growth regulation. Familial deficiency of this gene has been linked to an immunodeficiency associated with recurrent infectious diseases caused by bacteria, fungi and viruses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 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 |
---|---|---|---|---|---|---|---|
CD53 | NM_000560.4 | c.424C>G | p.Leu142Val | missense_variant, splice_region_variant | 6/8 | ENST00000271324.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CD53 | ENST00000271324.6 | c.424C>G | p.Leu142Val | missense_variant, splice_region_variant | 6/8 | 1 | NM_000560.4 | P1 | |
CD53 | ENST00000648608.1 | c.424C>G | p.Leu142Val | missense_variant, splice_region_variant | 7/9 | P1 | |||
CD53 | ENST00000476408.1 | n.366-2471C>G | intron_variant, non_coding_transcript_variant | 5 | |||||
CD53 | ENST00000497404.1 | n.189+1598C>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152158Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249130Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134790
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459740Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726246
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74318
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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 | Jul 26, 2021 | The c.424C>G (p.L142V) alteration is located in exon 7 (coding exon 5) of the CD53 gene. This alteration results from a C to G substitution at nucleotide position 424, causing the leucine (L) at amino acid position 142 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
Polyphen
D;D
Vest4
0.45
MVP
0.78
MPC
0.50
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at