3-52503070-T-A
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_015136.3(STAB1):c.655T>A(p.Cys219Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000156 in 1,601,656 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 (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
STAB1
NM_015136.3 missense
NM_015136.3 missense
Scores
11
6
2
Clinical Significance
Conservation
PhyloP100: 4.00
Genes affected
STAB1 (HGNC:18628): (stabilin 1) This gene encodes a large, transmembrane receptor protein which may function in angiogenesis, lymphocyte homing, cell adhesion, or receptor scavenging. The protein contains 7 fasciclin, 16 epidermal growth factor (EGF)-like, and 2 laminin-type EGF-like domains as well as a C-type lectin-like hyaluronan-binding Link module. The protein is primarily expressed on sinusoidal endothelial cells of liver, spleen, and lymph node. The receptor has been shown to endocytose ligands such as low density lipoprotein, Gram-positive and Gram-negative bacteria, and advanced glycosylation end products. Supporting its possible role as a scavenger receptor, the protein rapidly cycles between the plasma membrane and early endosomes. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.985
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STAB1 | NM_015136.3 | c.655T>A | p.Cys219Ser | missense_variant | 7/69 | ENST00000321725.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STAB1 | ENST00000321725.10 | c.655T>A | p.Cys219Ser | missense_variant | 7/69 | 1 | NM_015136.3 | P1 | |
STAB1 | ENST00000481607.1 | n.710T>A | non_coding_transcript_exon_variant | 7/21 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152076Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000133 AC: 3AN: 226122Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 122682
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GnomAD4 exome AF: 0.0000131 AC: 19AN: 1449580Hom.: 0 Cov.: 33 AF XY: 0.0000139 AC XY: 10AN XY: 719844
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GnomAD4 genome AF: 0.0000395 AC: 6AN: 152076Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74294
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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 | Sep 29, 2023 | The c.655T>A (p.C219S) alteration is located in exon 7 (coding exon 7) of the STAB1 gene. This alteration results from a T to A substitution at nucleotide position 655, causing the cysteine (C) at amino acid position 219 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
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of glycosylation at C219 (P = 0.0247);
MVP
MPC
ClinPred
D
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