17-74695151-A-G

Variant names:

• chr17-74695151-A-G
• NM_139018.5:c.818T>C

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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
• Publications: 0 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: 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=0.04675889).

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.818T>C	p.Leu273Pro	missense	Exon 7 of 7	NP_620587.2
	CD300LF	NM_001289084.2		c.863T>C	p.Leu288Pro	missense	Exon 7 of 7	NP_001276013.1	J3KS52
	CD300LF	NM_001289085.2		c.827T>C	p.Leu276Pro	missense	Exon 8 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.818T>C	p.Leu273Pro	missense	Exon 7 of 7	ENSP00000327075.6	Q8TDQ1-1
	CD300LF	ENST00000464910.5	TSL:1	c.827T>C	p.Leu276Pro	missense	Exon 7 of 7	ENSP00000464257.1	Q8TDQ1-6
	CD300LF	ENST00000469092.5	TSL:1	c.*129T>C		3_prime_UTR	Exon 7 of 7	ENSP00000463743.1	Q8TDQ1-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.9
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.026
Sift	Benign	0.055	T
Sift4G	Benign	0.28	T
Polyphen		0.0	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

Other links and lift over

hg19: chr17-72691290;