9-5361772-G-C

Position:

• chr9-5361772-G-C

Variant summary

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

The NM_018465.4(PLGRKT):​c.198C>G​(p.Ile66Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLGRKT NM_018465.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0340

Genes affected

PLGRKT (HGNC:23633): (plasminogen receptor with a C-terminal lysine) Predicted to be involved in positive regulation of plasminogen activation. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLGRKT	NM_018465.4	c.198C>G	p.Ile66Met	missense_variant	4/6	ENST00000223864.7
PLGRKT	XM_005251510.6	c.198C>G	p.Ile66Met	missense_variant	4/6
PLGRKT	XM_011517960.3	c.198C>G	p.Ile66Met	missense_variant	4/6
PLGRKT	XM_005251512.5	c.99C>G	p.Ile33Met	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLGRKT	ENST00000223864.7	c.198C>G	p.Ile66Met	missense_variant	4/6	1	NM_018465.4	P1
PLGRKT	ENST00000482696.5	n.578C>G		non_coding_transcript_exon_variant	5/5	3
PLGRKT	ENST00000472145.5			downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Feb 17, 2022

The c.198C>G (p.I66M) alteration is located in exon 4 (coding exon 2) of the PLGRKT gene. This alteration results from a C to G substitution at nucleotide position 198, causing the isoleucine (I) at amino acid position 66 to be replaced by a methionine (M). 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	0.11
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0064	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	0.93	D
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.097
Sift	Benign	0.032	D
Sift4G	Uncertain	0.018	D
Polyphen		0.66	P
Vest4		0.50
MutPred		0.63		Gain of catalytic residue at I66 (P = 0.081);
MVP		0.23
MPC		0.011
ClinPred		0.94	D
GERP RS		3.4
Varity_R		0.11
gMVP		0.57

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: chr9-5361772;