7-100399797-G-C

Variant names:

• chr7-100399797-G-C
• rs201973358
• NM_013439.3:c.802G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_013439.3(PILRA):​c.802G>C​(p.Val268Leu) 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. 15/24 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V268F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PILRA NM_013439.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 1 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]

ENSG00000289690 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.802G>C	p.Val268Leu	missense	Exon 7 of 7	NP_038467.2
	PILRA	NM_178272.2		c.583G>C	p.Val195Leu	missense	Exon 6 of 6	NP_840056.1	Q9UKJ1-3
	PILRA	NM_178273.2		c.*21G>C		3_prime_UTR	Exon 5 of 5	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.802G>C	p.Val268Leu	missense	Exon 7 of 7	ENSP00000198536.2	Q9UKJ1-1
	PILRA	ENST00000350573.2	TSL:1	c.583G>C	p.Val195Leu	missense	Exon 6 of 6	ENSP00000340109.2	Q9UKJ1-3
	PILRA	ENST00000394000.6	TSL:1	c.*21G>C		3_prime_UTR	Exon 5 of 5	ENSP00000377569.2	Q9UKJ1-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.029
DANN	Benign	0.55
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0049	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		-1.0
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.041
Sift	Benign	0.40	T
Sift4G	Benign	1.0	T
Polyphen		0.010	B
Vest4		0.071
MutPred		0.15		Loss of catalytic residue at V268 (P = 0.0648)
MVP		0.17
MPC		0.22
ClinPred		0.025	T
GERP RS		-5.0
Varity_R		0.026
gMVP		0.12
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: 26

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

Other links and lift over

dbSNP: rs201973358; hg19: chr7-99997420;