19-43581572-C-T

Variant names:

• chr19-43581572-C-T
• rs1972933154
• NM_001193621.3:c.350C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001193621.3(PINLYP):​c.350C>T​(p.Thr117Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000013 in 1,535,364 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: PINLYP NM_001193621.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.717
• Publications: 0 publications found

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]

ENSG00000268361 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0984157).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193621.3. 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
	PINLYP	NM_001193621.3	MANE Select	c.350C>T	p.Thr117Ile	missense	Exon 5 of 6	NP_001180550.2	A6NC86-1
	PINLYP	NM_001193622.2		c.86C>T	p.Thr29Ile	missense	Exon 3 of 4	NP_001180551.1	A6NC86-4
	PINLYP	NM_001321124.2		c.86C>T	p.Thr29Ile	missense	Exon 3 of 4	NP_001308053.1	A6NC86-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PINLYP	ENST00000599207.6	TSL:5 MANE Select	c.350C>T	p.Thr117Ile	missense	Exon 5 of 6	ENSP00000469886.1	A6NC86-1
	PINLYP	ENST00000562255.5	TSL:1	c.86C>T	p.Thr29Ile	missense	Exon 3 of 4	ENSP00000457623.1	A6NC86-4
	ENSG00000268361	ENST00000594374.1	TSL:3	c.168+11296G>A		intron	N/A	ENSP00000472698.1	M0R2N6

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383178 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 682494

African (AFR) AF: 0.00 AC: 0 AN: 31560

American (AMR) AF: 0.00 AC: 0 AN: 35488

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25076

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078404

Other (OTH) AF: 0.00 AC: 0 AN: 58012

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74346

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

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	0.13
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.86
DEOGEN2	Benign	0.0088	T
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.098	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.72
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.0	N
Sift	Benign	0.26	T
Sift4G	Benign	0.10	T
Polyphen		0.52	P
Vest4		0.038
MVP		0.34
GERP RS		2.9
Varity_R		0.038
gMVP		0.49
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs1972933154; hg19: chr19-44085724;