17-43853884-A-G

Variant names:

• chr17-43853884-A-G
• NM_145273.4:c.559A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_145273.4(CD300LG):​c.559A>G​(p.Thr187Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD300LG NM_145273.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0970

Genes affected

CD300LG (HGNC:30455): (CD300 molecule like family member g) Members of the CD300 (see MIM 606786)-like (CD300L) family, such as CD300LG, are widely expressed on hematopoietic cells. All CD300L proteins are type I cell surface glycoproteins that contain a single immunoglobulin (Ig) V-like domain (Takatsu et al., 2006 [PubMed 16876123]).[supplied by OMIM, Mar 2008]

LOC107985077 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a glycosylation_site O-linked (GalNAc...) threonine (size 0) in uniprot entity CLM9_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09037396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD300LG	NM_145273.4	c.559A>G	p.Thr187Ala	missense_variant	Exon 4 of 7	ENST00000317310.5	NP_660316.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD300LG	ENST00000317310.5	c.559A>G	p.Thr187Ala	missense_variant	Exon 4 of 7	1	NM_145273.4	ENSP00000321005.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.559A>G (p.T187A) alteration is located in exon 4 (coding exon 4) of the CD300LG gene. This alteration results from a A to G substitution at nucleotide position 559, causing the threonine (T) at amino acid position 187 to be replaced by an alanine (A). 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	Benign	0.080
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.9
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	.;.;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.40	T;T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.090	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	.;L;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.043
Sift	Benign	0.065	T;T;T
Sift4G	Benign	0.13	T;D;T
Polyphen		0.40	.;.;B
Vest4		0.053
MutPred		0.16		.;Loss of glycosylation at T187 (P = 0.0134);Loss of glycosylation at T187 (P = 0.0134);
MVP		0.18
MPC		0.042
ClinPred		0.44	T
GERP RS		2.7
Varity_R		0.052
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-41931252;