17-74612742-C-A

Variant names:

• chr17-74612742-C-A
• rs113824696
• NM_181449.3:c.529G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181449.3(CD300E):​c.529G>T​(p.Val177Leu) 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V177M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD300E NM_181449.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.738
• Publications: 1 publications found

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]

CD300LD-AS1 (HGNC:26480): (CD300LD antisense RNA 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

LOC101928343 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06273988).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181449.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD300E	NM_181449.3	MANE Select	c.529G>T	p.Val177Leu	missense	Exon 4 of 4	NP_852114.2	Q496F6
	LOC101928343	NR_158152.1		n.2503+6116C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD300E	ENST00000392619.2	TSL:1 MANE Select	c.529G>T	p.Val177Leu	missense	Exon 4 of 4	ENSP00000376395.2	Q496F6
	CD300E	ENST00000412268.2	TSL:3	c.535G>T	p.Val179Leu	missense	Exon 4 of 4	ENSP00000415488.2	C9JDD2
	CD300E	ENST00000961099.1		c.181G>T	p.Val61Leu	missense	Exon 3 of 3	ENSP00000631158.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.16
DANN	Benign	0.75
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-2.3	N
PhyloP100		0.74
PrimateAI	Benign	0.31	T
REVEL	Benign	0.025
Sift4G	Benign	1.0	T
Polyphen		0.0070	B
Vest4		0.056
MutPred		0.40		Loss of sheet (P = 0.0054)
MVP		0.15
ClinPred		0.055	T
GERP RS		1.1
Varity_R		0.032
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs113824696; hg19: chr17-72608881;