17-74617458-C-G

Position:

• chr17-74617458-C-G

Variant summary

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

The NM_181449.3(CD300E):​c.48G>C​(p.Leu16Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,218 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CD300E NM_181449.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.75

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]

LOC101928343 (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=0.049087495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD300E	NM_181449.3	c.48G>C	p.Leu16Phe	missense_variant	2/4	ENST00000392619.2
LOC101928343	NR_158152.1	n.2504-8069C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD300E	ENST00000392619.2	c.48G>C	p.Leu16Phe	missense_variant	2/4	1	NM_181449.3	P1
CD300E	ENST00000412268.1	c.54G>C	p.Leu18Phe	missense_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1459218 Hom.: 0 Cov.: 33 AF XY: 0.00000551 AC XY: 4 AN XY: 725848

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

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

Jun 13, 2023

The c.48G>C (p.L16F) alteration is located in exon 2 (coding exon 2) of the CD300E gene. This alteration results from a G to C substitution at nucleotide position 48, causing the leucine (L) at amino acid position 16 to be replaced by a phenylalanine (F). 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	0.074
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.7
DANN	Benign	0.39
DEOGEN2	Benign	0.024	T;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.22	T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.049	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.79	N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.26	.;N
REVEL	Benign	0.041
Sift	Benign	0.64	.;T
Sift4G	Benign	0.70	T;.
Polyphen		0.55	P;.
Vest4		0.085
MutPred		0.50		Gain of loop (P = 0.0045);.;
MVP		0.085
ClinPred		0.14	T
GERP RS		-0.46
Varity_R		0.043
gMVP		0.079

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr17-72613597;