17-74695151-A-G

Position:

• chr17-74695151-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_139018.5(CD300LF):​c.818T>C​(p.Leu273Pro) 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. 15/21 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: CD300LF NM_139018.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.85

Genes affected

CD300LF (HGNC:29883): (CD300 molecule like family member f) This gene encodes a member of the CD300 protein family. Members of this family are cell surface glycoproteins with a single IgV-like extracellular domain, and are involved in the regulation of immune response. The encoded protein is an inhibitory receptor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

RAB37 (HGNC:30268): (RAB37, member RAS oncogene family) Rab proteins are low molecular mass GTPases that are critical regulators of vesicle trafficking. For additional background information on Rab proteins, see MIM 179508.[supplied by OMIM, Apr 2006]

CD300LF (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04675889).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD300LF	NM_139018.5	c.818T>C	p.Leu273Pro	missense_variant	7/7	ENST00000326165.11	NP_620587.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD300LF	ENST00000326165.11	c.818T>C	p.Leu273Pro	missense_variant	7/7	1	NM_139018.5	ENSP00000327075.6

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.818T>C (p.L273P) alteration is located in exon 7 (coding exon 7) of the CD300LF gene. This alteration results from a T to C substitution at nucleotide position 818, causing the leucine (L) at amino acid position 273 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	0.073
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.21
DANN	Benign	0.50
DEOGEN2	Benign	0.067	T;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.23	T;T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.047	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.92	N;.;.
REVEL	Benign	0.026
Sift	Benign	0.055	T;.;.
Sift4G	Benign	0.28	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.073
MutPred		0.18		Gain of glycosylation at L273 (P = 0.0418);.;.;
MVP		0.12
MPC		0.16
ClinPred		0.081	T
GERP RS		-7.5
Varity_R		0.13
gMVP		0.15

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: chr17-72691290;