Genetic Variant PINLYP:p.Thr70Ile (chr19-43581233-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001193621.3(PINLYP):c.209C>T(p.Thr70Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,384,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 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)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

PINLYP
NM_001193621.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.838

Publications

0 publications found

Variant links:

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]

PINLYP links:

ENSG00000268361 (HGNC:):

ENSG00000268361 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13506827).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PINLYP	NM_001193621.3	MANE Select	c.209C>T	p.Thr70Ile	missense	Exon 4 of 6	NP_001180550.2	A6NC86-1
PINLYP	NM_001193622.2		c.-56C>T		5_prime_UTR	Exon 2 of 4	NP_001180551.1	A6NC86-4
PINLYP	NM_001321124.2		c.-56C>T		5_prime_UTR	Exon 2 of 4	NP_001308053.1	A6NC86-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PINLYP	ENST00000599207.6	TSL:5 MANE Select	c.209C>T	p.Thr70Ile	missense	Exon 4 of 6	ENSP00000469886.1	A6NC86-1
PINLYP	ENST00000562255.5	TSL:1	c.-56C>T		5_prime_UTR	Exon 2 of 4	ENSP00000457623.1	A6NC86-4
ENSG00000268361	ENST00000594374.1	TSL:3	c.168+11635G>A		intron	N/A	ENSP00000472698.1	M0R2N6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000285

AC:

AN:

140236

AF XY:

0.0000265

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000101

AC:

AN:

1384782

Hom.:

Cov.:

AF XY:

0.0000132

AC XY:

AN XY:

683324

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31594

American (AMR)

AF:

0.00

AC:

AN:

35694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.000177

AC:

AN:

79232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34752

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078938

Other (OTH)

AF:

0.00

AC:

AN:

57962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.039

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.42

M_CAP

Benign

0.019

MetaRNN

Benign

0.14

MutationAssessor

Benign

1.5

PhyloP100

0.84

PrimateAI

Benign

0.43

Sift4G

Uncertain

0.0060

Vest4

0.25

MVP

0.38

GERP RS

1.6

PromoterAI

0.030

Neutral

(source)

Varity_R

0.056

gMVP

0.67

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over