Genetic Variant NM_001193621.3:c.120T>C (chr19-43578639-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001193621.3(PINLYP):c.120T>C(p.His40His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,535,434 control chromosomes in the GnomAD database, including 92,651 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 0.30 ( 7154 hom., cov: 32)

Exomes 𝑓: 0.35 ( 85497 hom. )

Consequence

PINLYP
NM_001193621.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.597

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP7

Synonymous conserved (PhyloP=-0.597 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PINLYP	NM_001193621.3 link	c.120T>C	p.His40His	synonymous_variant	Exon 3 of 6	ENST00000599207.6	NP_001180550.2	A6NC86-1
PINLYP	XM_047438830.1 link	c.192T>C	p.His64His	synonymous_variant	Exon 2 of 5		XP_047294786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PINLYP	ENST00000599207.6 link	c.120T>C	p.His40His	synonymous_variant	Exon 3 of 6	5	NM_001193621.3	ENSP00000469886.1		A6NC86-1
ENSG00000268361	ENST00000594374.1 link	c.168+14229A>G		intron_variant	Intron 1 of 2	3		ENSP00000472698.1		M0R2N6

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45614

AN:

151918

Hom.:

7145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.310

Gnomad ASJ

AF:

0.387

Gnomad EAS

AF:

0.271

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.291

GnomAD3 exomes

AF:

0.322

AC:

43342

AN:

134524

Hom.:

7223

AF XY:

0.328

AC XY:

24053

AN XY:

73272

show subpopulations

Gnomad AFR exome

AF:

0.194

Gnomad AMR exome

AF:

0.268

Gnomad ASJ exome

AF:

0.360

Gnomad EAS exome

AF:

0.267

Gnomad SAS exome

AF:

0.348

Gnomad FIN exome

AF:

0.325

Gnomad NFE exome

AF:

0.356

Gnomad OTH exome

AF:

0.329

GnomAD4 exome

AF:

0.349

AC:

482501

AN:

1383398

Hom.:

85497

Cov.:

AF XY:

0.348

AC XY:

237881

AN XY:

682662

show subpopulations

Gnomad4 AFR exome

AF:

0.190

Gnomad4 AMR exome

AF:

0.274

Gnomad4 ASJ exome

AF:

0.371

Gnomad4 EAS exome

AF:

0.266

Gnomad4 SAS exome

AF:

0.348

Gnomad4 FIN exome

AF:

0.318

Gnomad4 NFE exome

AF:

0.361

Gnomad4 OTH exome

AF:

0.331

GnomAD4 genome

AF:

0.300

AC:

45634

AN:

152036

Hom.:

7154

Cov.:

AF XY:

0.297

AC XY:

22072

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.194

Gnomad4 AMR

AF:

0.310

Gnomad4 ASJ

AF:

0.387

Gnomad4 EAS

AF:

0.270

Gnomad4 SAS

AF:

0.346

Gnomad4 FIN

AF:

0.311

Gnomad4 NFE

AF:

0.355

Gnomad4 OTH

AF:

0.294

Alfa

AF:

0.285

Hom.:

1766

Bravo

AF:

0.294

Asia WGS

AF:

0.294

AC:

1023

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.66

DANN

Benign

0.47

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.

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