chr19-43576907-G-GGGCC

Variant names:

• chr19-43576907-G-GGGCC
• rs3213239
• NM_001193621.3:c.-88_-85dupGCCG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001193621.3(PINLYP):​c.-88_-85dupGCCG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.63 (30159 hom., cov: 0)
  • Exomes 𝑓: 0.62 (55683 hom.)
• Consequence: PINLYP NM_001193621.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 21 publications found

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]

ENSG00000268361 (HGNC:):

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)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PINLYP	NM_001193621.3	c.-88_-85dupGCCG		5_prime_UTR_variant	Exon 1 of 6	ENST00000599207.6	NP_001180550.2
PINLYP	XM_047438830.1	c.-211_-208dupGCCG		5_prime_UTR_variant	Exon 1 of 5		XP_047294786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PINLYP	ENST00000599207.6	c.-88_-85dupGCCG		5_prime_UTR_variant	Exon 1 of 6	5	NM_001193621.3	ENSP00000469886.1
ENSG00000268361	ENST00000594374.1	c.169-15891_169-15888dupGGCC		intron_variant	Intron 1 of 2	3		ENSP00000472698.1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95042 AN: 151248 Hom.: 30144 Cov.: 0

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.705

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.641

GnomAD4 exome AF: 0.616 AC: 172214 AN: 279460 Hom.: 55683 Cov.: 4 AF XY: 0.613 AC XY: 89371 AN XY: 145734

African (AFR) AF: 0.616 AC: 5076 AN: 8238

American (AMR) AF: 0.755 AC: 8182 AN: 10830

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 6254 AN: 9404

East Asian (EAS) AF: 0.889 AC: 18911 AN: 21282

South Asian (SAS) AF: 0.598 AC: 12082 AN: 20218

European-Finnish (FIN) AF: 0.543 AC: 10046 AN: 18514

Middle Eastern (MID) AF: 0.712 AC: 939 AN: 1318

European-Non Finnish (NFE) AF: 0.580 AC: 100117 AN: 172558

Other (OTH) AF: 0.620 AC: 10607 AN: 17098

GnomAD4 genome AF: 0.628 AC: 95104 AN: 151366 Hom.: 30159 Cov.: 0 AF XY: 0.630 AC XY: 46602 AN XY: 73940

African (AFR) AF: 0.634 AC: 26149 AN: 41224

American (AMR) AF: 0.729 AC: 11089 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2346 AN: 3466

East Asian (EAS) AF: 0.881 AC: 4495 AN: 5104

South Asian (SAS) AF: 0.644 AC: 3094 AN: 4806

European-Finnish (FIN) AF: 0.555 AC: 5802 AN: 10462

Middle Eastern (MID) AF: 0.697 AC: 202 AN: 290

European-Non Finnish (NFE) AF: 0.591 AC: 40039 AN: 67794

Other (OTH) AF: 0.642 AC: 1351 AN: 2104

Alfa AF: 0.477 Hom.: 1258

Bravo AF: 0.647

Asia WGS AF: 0.744 AC: 2583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3213239; hg19: chr19-44081059;