rs3741851

chr12-9150844-A-Gchr12-9150844-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002864.3(PZP):c.4282-98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 773,852 control chromosomes in the GnomAD database, including 16,373 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 0.18 (2895 hom., cov: 32)
  • Exomes 𝑓: 0.19 (13478 hom.)
• Consequence: PZP NM_002864.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

Genes affected

PZP (HGNC:9750): (PZP alpha-2-macroglobulin like) The protein encoded by this gene is highly expressed in late-pregnancy serum and is similar in structure to alpha-2-macroglobulin. The encoded protein, which acts as a homotetramer, inhibits the activity of all four classes of proteinases. This protein contains cleavage sites for several proteinases. Upon binding of a proteinase, the conformation of this protein changes to trap the proteinase, limiting its activity. This protein appears to be elevated in the sera of presymptomatic Alzheimer's disease patients. [provided by RefSeq, Dec 2016]

KLRG1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PZP	NM_002864.3	c.4282-98T>C		intron_variant		ENST00000261336.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PZP	ENST00000261336.7	c.4282-98T>C		intron_variant		1	NM_002864.3	P1
PZP	ENST00000535230.5	c.*3751-98T>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27717 AN: 152054 Hom.: 2893 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.193 AC: 120242 AN: 621680 Hom.: 13478 AF XY: 0.198 AC XY: 66431 AN XY: 334692

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.249

Gnomad4 ASJ exome AF: 0.192

Gnomad4 EAS exome AF: 0.404

Gnomad4 SAS exome AF: 0.292

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.182 AC: 27718 AN: 152172 Hom.: 2895 Cov.: 32 AF XY: 0.188 AC XY: 13955 AN XY: 74388

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.217

Alfa AF: 0.177 Hom.: 5020

Bravo AF: 0.189

Asia WGS AF: 0.344 AC: 1193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.49
Dann	Benign	0.51

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

Other links and lift over

dbSNP: rs3741851; hg19: chr12-9303440; COSMIC: COSV54356588;