chr19-43577168-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001193621.3(PINLYP):c.-24C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000166 in 1,535,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

PINLYP
NM_001193621.3 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.416

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:

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 Gene-Disease associations (from GenCC):

head and neck cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
spinocerebellar ataxia, autosomal recessive 26
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

XRCC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.067976385).

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.-24C>T		5_prime_UTR	Exon 2 of 6	NP_001180550.2	A6NC86-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PINLYP	ENST00000599207.6	TSL:5 MANE Select	c.-24C>T		5_prime_UTR	Exon 2 of 6	ENSP00000469886.1	A6NC86-1
ENSG00000268361	ENST00000594374.1	TSL:3	c.168+15700G>A		intron	N/A	ENSP00000472698.1	M0R2N6
PINLYP	ENST00000612042.4	TSL:5	c.49C>T	p.Pro17Ser	missense	Exon 2 of 6	ENSP00000479240.1	A6NC86-2

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000892

AC:

AN:

134542

AF XY:

0.0000955

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:

0.000227

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000175

AC:

242

AN:

1383698

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

118

AN XY:

682798

show subpopulations

African (AFR)

AF:

0.0000317

AC:

AN:

31590

American (AMR)

AF:

0.00

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25178

East Asian (EAS)

AF:

0.00

AC:

AN:

35732

South Asian (SAS)

AF:

0.00

AC:

AN:

79232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33894

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.000221

AC:

238

AN:

1078786

Other (OTH)

AF:

0.0000518

AC:

AN:

57896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

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

AF:

0.0000854

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.000117

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

Benign

0.085

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.36

CADD

Benign

6.2

(source)

DANN

Benign

0.97

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.32

MetaRNN

Benign

0.068

MetaSVM

Benign

-0.88

PhyloP100

0.42

PrimateAI

Benign

0.24

Sift4G

Pathogenic

0.0

Vest4

0.091

MVP

0.072

ClinPred

0.25

GERP RS

3.5

PromoterAI

0.020

Neutral

(source)

gMVP

0.64

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over