Genetic Variant PINLYP:c.-56A>G (chr19-43577136-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001193621.3(PINLYP):c.-56A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 1,535,394 control chromosomes in the GnomAD database, including 481,132 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.80 ( 49341 hom., cov: 29)

Exomes 𝑓: 0.79 ( 431791 hom. )

Consequence

PINLYP
NM_001193621.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.26

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:

XRCC1 (HGNC:12828): (X-ray repair cross complementing 1) The protein encoded by this gene is involved in the efficient repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. This protein interacts with DNA ligase III, polymerase beta and poly (ADP-ribose) polymerase to participate in the base excision repair pathway. It may play a role in DNA processing during meiogenesis and recombination in germ cells. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]

XRCC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.5421614E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PINLYP	NM_001193621.3 link	c.-56A>G		5_prime_UTR_variant	Exon 2 of 6	ENST00000599207.6	NP_001180550.2	A6NC86-1
PINLYP	XM_047438830.1 link	c.17A>G	p.His6Arg	missense_variant	Exon 1 of 5		XP_047294786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PINLYP	ENST00000599207 link	c.-56A>G		5_prime_UTR_variant	Exon 2 of 6	5	NM_001193621.3	ENSP00000469886.1		A6NC86-1
ENSG00000268361	ENST00000594374.1 link	c.168+15732T>C		intron_variant	Intron 1 of 2	3		ENSP00000472698.1		M0R2N6

Frequencies

GnomAD3 genomes

AF:

0.805

AC:

122261

AN:

151898

Hom.:

49314

Cov.:

show subpopulations

Gnomad AFR

AF:

0.826

Gnomad AMI

AF:

0.838

Gnomad AMR

AF:

0.870

Gnomad ASJ

AF:

0.815

Gnomad EAS

AF:

0.883

Gnomad SAS

AF:

0.775

Gnomad FIN

AF:

0.736

Gnomad MID

AF:

0.854

Gnomad NFE

AF:

0.783

Gnomad OTH

AF:

0.812

GnomAD3 exomes

AF:

0.817

AC:

109751

AN:

134352

Hom.:

45053

AF XY:

0.811

AC XY:

59295

AN XY:

73144

show subpopulations

Gnomad AFR exome

AF:

0.826

Gnomad AMR exome

AF:

0.903

Gnomad ASJ exome

AF:

0.809

Gnomad EAS exome

AF:

0.884

Gnomad SAS exome

AF:

0.777

Gnomad FIN exome

AF:

0.747

Gnomad NFE exome

AF:

0.787

Gnomad OTH exome

AF:

0.823

GnomAD4 exome

AF:

0.789

AC:

1091588

AN:

1383378

Hom.:

431791

Cov.:

AF XY:

0.788

AC XY:

537711

AN XY:

682630

show subpopulations

Gnomad4 AFR exome

AF:

0.823

Gnomad4 AMR exome

AF:

0.898

Gnomad4 ASJ exome

AF:

0.817

Gnomad4 EAS exome

AF:

0.893

Gnomad4 SAS exome

AF:

0.779

Gnomad4 FIN exome

AF:

0.737

Gnomad4 NFE exome

AF:

0.782

Gnomad4 OTH exome

AF:

0.800

GnomAD4 genome

AF:

0.805

AC:

122344

AN:

152016

Hom.:

49341

Cov.:

AF XY:

0.805

AC XY:

59820

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.825

Gnomad4 AMR

AF:

0.871

Gnomad4 ASJ

AF:

0.815

Gnomad4 EAS

AF:

0.883

Gnomad4 SAS

AF:

0.775

Gnomad4 FIN

AF:

0.736

Gnomad4 NFE

AF:

0.783

Gnomad4 OTH

AF:

0.811

Alfa

AF:

0.791

Hom.:

67811

Bravo

AF:

0.821

TwinsUK

AF:

0.787

AC:

2920

ALSPAC

AF:

0.771

AC:

2973

ExAC

AF:

0.758

AC:

10975

Asia WGS

AF:

0.808

AC:

2808

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.74

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.0065

LIST_S2

Benign

0.20

MetaRNN

Benign

6.5e-7

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.32

Sift4G

Benign

1.0

Vest4

0.028

ClinPred

0.061

GERP RS

0.73

gMVP

0.44

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over