17-43853012-G-T

Variant names:

• chr17-43853012-G-T
• rs761211541
• NM_145273.4:c.480G>T

Variant summary

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

The NM_145273.4(CD300LG):​c.480G>T​(p.Leu160Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/26 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CD300LG NM_145273.4 missense, splice_region
• Scores: Splicing: ADA: 0.0001764
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216
• 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]

LOC107985077 (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=0.05362782).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD300LG	NM_145273.4	c.480G>T	p.Leu160Phe	missense_variant, splice_region_variant	Exon 3 of 7	ENST00000317310.5	NP_660316.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD300LG	ENST00000317310.5	c.480G>T	p.Leu160Phe	missense_variant, splice_region_variant	Exon 3 of 7	1	NM_145273.4	ENSP00000321005.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456474 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724462

African (AFR) AF: 0.00 AC: 0 AN: 33302

American (AMR) AF: 0.00 AC: 0 AN: 44024

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26030

East Asian (EAS) AF: 0.00 AC: 0 AN: 39212

South Asian (SAS) AF: 0.00 AC: 0 AN: 85202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109376

Other (OTH) AF: 0.00 AC: 0 AN: 60194

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	15
DANN	Benign	0.83
DEOGEN2	Benign	0.023	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.30	T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
PhyloP100		0.22
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.88	N;N
REVEL	Benign	0.065
Sift	Benign	0.15	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.97	.;D
Vest4		0.088
MutPred		0.17		Loss of glycosylation at P163 (P = 0.1668);Loss of glycosylation at P163 (P = 0.1668);
MVP		0.061
MPC		0.044
ClinPred		0.038	T
GERP RS		-0.49
Varity_R		0.050
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00018
dbscSNV1_RF	Benign	0.020
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.30		Position offset: 1

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

Other links and lift over

dbSNP: rs761211541; hg19: chr17-41930380;