17-74484085-G-A

Position:

• chr17-74484085-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_007261.4(CD300A):​c.859G>A​(p.Glu287Lys) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD300A NM_007261.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.79

Genes affected

CD300A (HGNC:19319): (CD300a molecule) This gene encodes a member of the CD300 glycoprotein family of cell surface proteins found on leukocytes involved in immune response signaling pathways. This gene is located on chromosome 17 in a cluster with all but one of the other family members. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03569606).
• BP6: Variant 17-74484085-G-A is Benign according to our data. Variant chr17-74484085-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3140512.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD300A	NM_007261.4	c.859G>A	p.Glu287Lys	missense_variant	7/7	ENST00000360141.8	NP_009192.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD300A	ENST00000360141.8	c.859G>A	p.Glu287Lys	missense_variant	7/7	1	NM_007261.4	ENSP00000353259	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.32
DANN	Benign	0.39
DEOGEN2	Benign	0.022	.;T;.;.;.;.
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.72	.;T;T;T;T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.036	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	.;L;.;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.66	.;N;N;N;N;.
REVEL	Benign	0.026
Sift	Benign	0.24	.;T;T;T;T;.
Sift4G	Benign	0.47	.;T;T;T;T;T
Polyphen		0.0050, 0.0	.;B;B;B;B;.
Vest4		0.13, 0.11, 0.20, 0.19, 0.12
MutPred		0.17		.;Gain of ubiquitination at E287 (P = 0.0016);.;.;.;.;
MVP		0.067
MPC		0.074
ClinPred		0.069	T
GERP RS		-5.5
Varity_R		0.033
gMVP		0.19

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: chr17-72480224;