rs766299098

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001193621.3(PINLYP):​c.157T>A​(p.Cys53Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000723 in 1,383,530 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C53R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000072 ( 1 hom. )

Consequence

PINLYP
NM_001193621.3 missense

Scores

5
4
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.04
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.948

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PINLYPNM_001193621.3 linkc.157T>A p.Cys53Ser missense_variant Exon 3 of 6 ENST00000599207.6 NP_001180550.2 A6NC86-1
PINLYPXM_047438830.1 linkc.229T>A p.Cys77Ser missense_variant Exon 2 of 5 XP_047294786.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PINLYPENST00000599207.6 linkc.157T>A p.Cys53Ser missense_variant Exon 3 of 6 5 NM_001193621.3 ENSP00000469886.1 A6NC86-1
ENSG00000268361ENST00000594374.1 linkc.168+14192A>T intron_variant Intron 1 of 2 3 ENSP00000472698.1 M0R2N6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000723
AC:
10
AN:
1383530
Hom.:
1
Cov.:
32
AF XY:
0.0000132
AC XY:
9
AN XY:
682726
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000507
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.46
D
BayesDel_noAF
Pathogenic
0.42
CADD
Uncertain
23
DANN
Benign
0.97
DEOGEN2
Uncertain
0.49
.;T
Eigen
Uncertain
0.32
Eigen_PC
Benign
0.19
FATHMM_MKL
Benign
0.72
D
LIST_S2
Benign
0.40
T;T
M_CAP
Uncertain
0.13
D
MetaRNN
Pathogenic
0.95
D;D
MetaSVM
Benign
-0.35
T
MutationAssessor
Uncertain
2.1
.;M
PrimateAI
Benign
0.40
T
Sift4G
Pathogenic
0.0
D;D
Vest4
0.87
MVP
0.39
ClinPred
0.54
D
GERP RS
4.0
Varity_R
0.29
gMVP
1.0

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

LitVar

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

Other links and lift over

dbSNP: rs766299098; hg19: chr19-44082828; API