chr7-100389909-G-A

Variant names:

• chr7-100389909-G-A
• NM_013439.3:c.476G>A

Variant summary

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

The NM_013439.3(PILRA):​c.476G>A​(p.Arg159Lys) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: PILRA NM_013439.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.773
• Publications: 0 publications found

Genes affected

PILRA (HGNC:20396): (paired immunoglobin like type 2 receptor alpha) Cell signaling pathways rely on a dynamic interaction between activating and inhibiting processes. SHP-1-mediated dephosphorylation of protein tyrosine residues is central to the regulation of several cell signaling pathways. Two types of inhibitory receptor superfamily members are immunoreceptor tyrosine-based inhibitory motif (ITIM)-bearing receptors and their non-ITIM-bearing, activating counterparts. Control of cell signaling via SHP-1 is thought to occur through a balance between PILRalpha-mediated inhibition and PILRbeta-mediated activation. These paired immunoglobulin-like receptor genes are located in a tandem head-to-tail orientation on chromosome 7. This particular gene encodes the ITIM-bearing member of the receptor pair, which functions in the inhibitory role. Alternative splicing has been observed at this locus and three variants, each encoding a distinct isoform, are described. [provided by RefSeq, Jul 2008]

ENSG00000287631 (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=0.044066936).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013439.3. 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
	PILRA	NM_013439.3	MANE Select	c.476G>A	p.Arg159Lys	missense	Exon 3 of 7	NP_038467.2
	PILRA	NM_178272.2		c.455-7970G>A		intron	N/A	NP_840056.1	Q9UKJ1-3
	PILRA	NM_178273.2		c.455-9382G>A		intron	N/A	NP_840057.1	Q9UKJ1-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PILRA	ENST00000198536.7	TSL:1 MANE Select	c.476G>A	p.Arg159Lys	missense	Exon 3 of 7	ENSP00000198536.2	Q9UKJ1-1
	PILRA	ENST00000350573.2	TSL:1	c.455-7970G>A		intron	N/A	ENSP00000340109.2	Q9UKJ1-3
	PILRA	ENST00000453419.5	TSL:1	c.455-7970G>A		intron	N/A	ENSP00000390026.1	C9JJ79

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

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	0.11
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.26
DANN	Benign	0.41
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.77
PrimateAI	Benign	0.19	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.014
Sift	Benign	0.43	T
Sift4G	Benign	0.62	T
Polyphen		0.43	B
Vest4		0.085
MutPred		0.19		Gain of ubiquitination at R159 (P = 0.0128)
MVP		0.33
MPC		0.20
ClinPred		0.15	T
GERP RS		-4.8
Varity_R		0.043
gMVP		0.29
Mutation Taster		=99/1	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

hg19: chr7-99987532;