17-74704696-C-T

Variant names:

• chr17-74704696-C-T
• rs199990109
• NM_139018.5:c.164G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_139018.5(CD300LF):​c.164G>A​(p.Arg55Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,614,198 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R55G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: CD300LF NM_139018.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.134
• Publications: 3 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016047567).

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.164G>A	p.Arg55Gln	missense	Exon 2 of 7	NP_620587.2
	CD300LF	NM_001289084.2		c.164G>A	p.Arg55Gln	missense	Exon 2 of 7	NP_001276013.1	J3KS52
	CD300LF	NM_001289085.2		c.173G>A	p.Arg58Gln	missense	Exon 3 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.164G>A	p.Arg55Gln	missense	Exon 2 of 7	ENSP00000327075.6	Q8TDQ1-1
	CD300LF	ENST00000464910.5	TSL:1	c.173G>A	p.Arg58Gln	missense	Exon 2 of 7	ENSP00000464257.1	Q8TDQ1-6
	CD300LF	ENST00000581500.1	TSL:1	c.173G>A	p.Arg58Gln	missense	Exon 2 of 5	ENSP00000464610.1	Q8TDQ1-2

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000386 AC: 97 AN: 251492 AF XY: 0.000390

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00645

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000211 AC: 308 AN: 1461890 Hom.: 1 Cov.: 30 AF XY: 0.000228 AC XY: 166 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00620 AC: 162 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000730 AC: 63 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000333 AC: 37 AN: 1112010

Other (OTH) AF: 0.000695 AC: 42 AN: 60396

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74476

African (AFR) AF: 0.0000241 AC: 1 AN: 41564

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00547 AC: 19 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000494 Hom.: 0

Bravo AF: 0.000215

ExAC AF: 0.000288 AC: 35

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

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	0.12
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Benign	-0.025
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.25	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.13
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.35
Sift	Benign	0.10	T
Sift4G	Uncertain	0.050	T
Polyphen		1.0	D
Vest4		0.28
MVP		0.80
MPC		0.47
ClinPred		0.13	T
GERP RS		-0.11
Varity_R		0.27
gMVP		0.83
Mutation Taster		=61/39	polymorphism

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: rs199990109; hg19: chr17-72700835; COSMIC: COSV56898071;