19-43581614-C-T

Variant names:

• chr19-43581614-C-T
• rs772077321
• NM_001193621.3:c.392C>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.392C>T​(p.Ala131Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000939 in 1,384,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 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. A131E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000094 (0 hom.)
• Consequence: PINLYP NM_001193621.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• 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=0.08876312).

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.392C>T	p.Ala131Val	missense	Exon 5 of 6	NP_001180550.2	A6NC86-1
	PINLYP	NM_001193622.2		c.128C>T	p.Ala43Val	missense	Exon 3 of 4	NP_001180551.1	A6NC86-4
	PINLYP	NM_001321124.2		c.128C>T	p.Ala43Val	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.392C>T	p.Ala131Val	missense	Exon 5 of 6	ENSP00000469886.1	A6NC86-1
	PINLYP	ENST00000562255.5	TSL:1	c.128C>T	p.Ala43Val	missense	Exon 3 of 4	ENSP00000457623.1	A6NC86-4
	ENSG00000268361	ENST00000594374.1	TSL:3	c.168+11254G>A		intron	N/A	ENSP00000472698.1	M0R2N6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000939 AC: 13 AN: 1384328 Hom.: 0 Cov.: 31 AF XY: 0.00000439 AC XY: 3 AN XY: 683080

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25172

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.0000252 AC: 2 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.0000102 AC: 11 AN: 1078988

Other (OTH) AF: 0.00 AC: 0 AN: 58046

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.10
DANN	Benign	0.90
DEOGEN2	Benign	0.038	T
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.089	T
MutationAssessor	Benign	0.79	N
PhyloP100		-1.0
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.2	N
Sift	Benign	0.25	T
Sift4G	Benign	0.34	T
Polyphen		0.047	B
Vest4		0.098
MVP		0.45
GERP RS		-6.7
Varity_R		0.017
gMVP		0.64
Mutation Taster		=95/5	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

dbSNP: rs772077321; hg19: chr19-44085766;