chr17-74617358-A-G
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_181449.3(CD300E):āc.148T>Cā(p.Cys50Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,924 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 (ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 32)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
CD300E
NM_181449.3 missense
NM_181449.3 missense
Scores
7
9
3
Clinical Significance
Conservation
PhyloP100: 3.56
Genes affected
CD300E (HGNC:28874): (CD300e molecule) This gene encodes a member of the CD300 glycoprotein family of cell surface proteins expressed on myeloid cells. The protein interacts with the TYRO protein tyrosine kinase-binding protein and is thought to act as an activating receptor. [provided by RefSeq, Nov 2012]
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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, 0.956
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CD300E | NM_181449.3 | c.148T>C | p.Cys50Arg | missense_variant | 2/4 | ENST00000392619.2 | |
LOC101928343 | NR_158152.1 | n.2504-8169A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CD300E | ENST00000392619.2 | c.148T>C | p.Cys50Arg | missense_variant | 2/4 | 1 | NM_181449.3 | P1 | |
CD300E | ENST00000412268.1 | c.154T>C | p.Cys52Arg | missense_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152040Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251454Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135912
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461884Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727242
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GnomAD4 genome AF: 0.0000395 AC: 6AN: 152040Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74254
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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 05, 2023 | The c.148T>C (p.C50R) alteration is located in exon 2 (coding exon 2) of the CD300E gene. This alteration results from a T to C substitution at nucleotide position 148, causing the cysteine (C) at amino acid position 50 to be replaced by an arginine (R). 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
Benign
DANN
Uncertain
DEOGEN2
Uncertain
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;D
REVEL
Uncertain
Sift
Uncertain
.;D
Sift4G
Pathogenic
D;.
Polyphen
D;.
Vest4
MVP
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