chr17-74695789-T-A

Variant names:

• chr17-74695789-T-A
• rs2034310
• NM_139018.5:c.653A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139018.5(CD300LF):​c.653A>T​(p.Gln218Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CD300LF NM_139018.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164
• Publications: 55 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07820541).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139018.5. 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
	CD300LF	NM_139018.5	MANE Select	c.653A>T	p.Gln218Leu	missense	Exon 6 of 7	NP_620587.2
	CD300LF	NM_001289084.2		c.698A>T	p.Gln233Leu	missense	Exon 6 of 7	NP_001276013.1	J3KS52
	CD300LF	NM_001289085.2		c.662A>T	p.Gln221Leu	missense	Exon 7 of 8	NP_001276014.1	Q8TDQ1-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD300LF	ENST00000326165.11	TSL:1 MANE Select	c.653A>T	p.Gln218Leu	missense	Exon 6 of 7	ENSP00000327075.6	Q8TDQ1-1
	CD300LF	ENST00000464910.5	TSL:1	c.662A>T	p.Gln221Leu	missense	Exon 6 of 7	ENSP00000464257.1	Q8TDQ1-6
	CD300LF	ENST00000581500.1	TSL:1	c.684A>T	p.Ala228Ala	synonymous	Exon 5 of 5	ENSP00000464610.1	Q8TDQ1-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 65

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.0
DANN	Benign	0.77
DEOGEN2	Benign	0.091	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.16
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.011
Sift	Benign	0.20	T
Sift4G	Benign	0.35	T
Polyphen		0.17	B
Vest4		0.18
MutPred		0.30		Gain of sheet (P = 0.0036)
MVP		0.35
MPC		0.12
ClinPred		0.035	T
GERP RS		-0.60
Varity_R		0.071
gMVP		0.19

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

Other links and lift over

dbSNP: rs2034310; hg19: chr17-72691928;