17-74542897-G-A

Position:

• chr17-74542897-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006678.5(CD300C):​c.491C>T​(p.Thr164Ile) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: CD300C NM_006678.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.889

Genes affected

CD300C (HGNC:19320): (CD300c molecule) The CMRF35 antigen, which was identified by reactivity with a monoclonal antibody, is present on monocytes, neutrophils, and some T and B lymphocytes (Jackson et al., 1992 [PubMed 1349532]).[supplied by OMIM, Mar 2008]

LOC107985074 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17900169).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD300C	NM_006678.5	c.491C>T	p.Thr164Ile	missense_variant	3/4	ENST00000330793.2	NP_006669.1
CD300C	XM_017024033.3	c.491C>T	p.Thr164Ile	missense_variant	3/5		XP_016879522.1
CD300C	XM_047435157.1	c.594C>T	p.Asp198=	synonymous_variant	3/4		XP_047291113.1
LOC107985074	XR_007065901.1	n.237-280G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD300C	ENST00000330793.2	c.491C>T	p.Thr164Ile	missense_variant	3/4	1	NM_006678.5	ENSP00000329507	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2023

The c.491C>T (p.T164I) alteration is located in exon 3 (coding exon 3) of the CD300C gene. This alteration results from a C to T substitution at nucleotide position 491, causing the threonine (T) at amino acid position 164 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.012
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.014	D
Polyphen		0.99	D
Vest4		0.061
MutPred		0.36		Gain of sheet (P = 0.0061);
MVP		0.32
MPC		0.32
ClinPred		0.54	D
GERP RS		1.1
Varity_R		0.097
gMVP		0.44

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-72539036;