17-74617280-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_181449.3(CD300E):​c.226G>A​(p.Val76Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

CD300E
NM_181449.3 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38
Variant links:
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]

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=0.3734562).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CD300ENM_181449.3 linkc.226G>A p.Val76Met missense_variant Exon 2 of 4 ENST00000392619.2 NP_852114.2 Q496F6B4E0V9
LOC101928343NR_158152.1 linkn.2504-8247C>T intron_variant Intron 3 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CD300EENST00000392619.2 linkc.226G>A p.Val76Met missense_variant Exon 2 of 4 1 NM_181449.3 ENSP00000376395.2 Q496F6
CD300EENST00000412268.1 linkc.232G>A p.Val78Met missense_variant Exon 2 of 2 3 ENSP00000415488.2 C9JDD2

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152210
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251460
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461890
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152210
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000264
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.226G>A (p.V76M) alteration is located in exon 2 (coding exon 2) of the CD300E gene. This alteration results from a G to A substitution at nucleotide position 226, causing the valine (V) at amino acid position 76 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
T;.
Eigen
Uncertain
0.28
Eigen_PC
Benign
0.10
FATHMM_MKL
Benign
0.32
N
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.37
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.5
M;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-3.0
.;D
REVEL
Benign
0.12
Sift
Uncertain
0.022
.;D
Sift4G
Uncertain
0.057
T;.
Polyphen
1.0
D;.
Vest4
0.33
MVP
0.33
ClinPred
0.90
D
GERP RS
3.9
Varity_R
0.29
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs142872832; hg19: chr17-72613419; COSMIC: COSV100151325; API