19-43581980-A-G

Variant summary

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

The NM_001193621.3(PINLYP):c.594A>G(p.Ile198Met) 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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PINLYP NM_001193621.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.38

Genes affected

PINLYP (HGNC:44206): (phospholipase A2 inhibitor and LY6/PLAUR domain containing) Predicted to enable phospholipase inhibitor activity. Predicted to be involved in negative regulation of catalytic activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0647977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PINLYP	NM_001193621.3	c.594A>G	p.Ile198Met	missense_variant	6/6	ENST00000599207.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PINLYP	ENST00000599207.6	c.594A>G	p.Ile198Met	missense_variant	6/6	5	NM_001193621.3	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Jan 05, 2022

The c.666A>G (p.I222M) alteration is located in exon 6 (coding exon 5) of the PINLYP gene. This alteration results from a A to G substitution at nucleotide position 666, causing the isoleucine (I) at amino acid position 222 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	0.075
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	0.15
Dann	Benign	0.71
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.37	T;T;.;.;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.065	T;T;T;T;T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.33	T
Sift4G	Benign	0.11	T;T;T;T;T
Vest4		0.13
MVP		0.28
GERP RS		-2.0
Varity_R		0.063
gMVP		0.80

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: chr19-44086132;