17-43853947-T-C

Variant names:

• chr17-43853947-T-C
• NM_145273.4:c.622T>C

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.622T>C​(p.Ser208Pro) 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. 13/21 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: 0.795

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...) serine (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=0.1540635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD300LG	NM_145273.4	c.622T>C	p.Ser208Pro	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.622T>C	p.Ser208Pro	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

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.622T>C (p.S208P) alteration is located in exon 4 (coding exon 4) of the CD300LG gene. This alteration results from a T to C substitution at nucleotide position 622, causing the serine (S) at amino acid position 208 to be replaced by a proline (P). 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	0.089
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	.;.;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.52	T;T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	.;L;L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.028
Sift	Uncertain	0.011	D;D;D
Sift4G	Uncertain	0.052	T;D;D
Polyphen		0.12	.;.;B
Vest4		0.21
MutPred		0.26		.;Gain of catalytic residue at S208 (P = 5e-04);Gain of catalytic residue at S208 (P = 5e-04);
MVP		0.35
MPC		0.088
ClinPred		0.24	T
GERP RS		1.7
Varity_R		0.22
gMVP		0.25

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: chr17-41931315;