17-43848758-C-G

Variant names:

• chr17-43848758-C-G
• rs72836561
• NM_145273.4:c.244C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145273.4(CD300LG):​c.244C>G​(p.Arg82Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CD300LG NM_145273.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282
• Publications: 0 publications found

Genes affected

CD300LG (HGNC:30455): (CD300 molecule like family member g) Members of the CD300 (see MIM 606786)-like (CD300L) family, such as CD300LG, are widely expressed on hematopoietic cells. All CD300L proteins are type I cell surface glycoproteins that contain a single immunoglobulin (Ig) V-like domain (Takatsu et al., 2006 [PubMed 16876123]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41549614).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145273.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD300LG	NM_145273.4	MANE Select	c.244C>G	p.Arg82Gly	missense	Exon 2 of 7	NP_660316.2
	CD300LG	NM_001168322.2		c.244C>G	p.Arg82Gly	missense	Exon 2 of 7	NP_001161794.1
	CD300LG	NM_001168323.2		c.244C>G	p.Arg82Gly	missense	Exon 2 of 6	NP_001161795.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD300LG	ENST00000317310.5	TSL:1 MANE Select	c.244C>G	p.Arg82Gly	missense	Exon 2 of 7	ENSP00000321005.3
	CD300LG	ENST00000539718.5	TSL:1	c.244C>G	p.Arg82Gly	missense	Exon 2 of 7	ENSP00000442368.1
	CD300LG	ENST00000293396.12	TSL:1	c.244C>G	p.Arg82Gly	missense	Exon 2 of 6	ENSP00000293396.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461850 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727218

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60392

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		0.28
PrimateAI	Benign	0.18	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.072
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.012	D
Polyphen		0.91	P
Vest4		0.23
MutPred		0.55		Loss of MoRF binding (P = 0.0151)
MVP		0.41
MPC		0.15
ClinPred		0.70	D
GERP RS		1.1
Varity_R		0.25
gMVP		0.38

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: rs72836561; hg19: chr17-41926126;