rs10845219

Positions:

• chr12-10825055-T-C

Variant summary

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

The ENST00000538332.2(PRH1):​c.*157A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 368,246 control chromosomes in the GnomAD database, including 62,146 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 0.51 (21800 hom., cov: 31)
  • Exomes 𝑓: 0.60 (40346 hom.)
• Consequence: PRH1 ENST00000538332.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500

Genes affected

PRH1 (HGNC:9366): (proline rich protein HaeIII subfamily 1) This gene encodes a member of the heterogeneous family of proline-rich salivary glycoproteins. The encoded preproprotein undergoes proteolytic processing to generate one or more mature isoforms before secretion from the parotid and submandibular/sublingual glands. Multiple distinct alleles of this locus including the parotid isoelectric-focusing variant slow (PIF-s), the parotid acidic protein (Pa), and the double band slow (Db-s) isoforms have been characterized. The reference genome encodes the Db-s allele. Certain alleles of this gene are associated with susceptibility to dental caries. This gene is located in a cluster of closely related salivary proline-rich proteins on chromosome 12. Co-transcription of this gene with adjacent genes has been observed. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRH1	ENST00000538332.2	c.*157A>G		3_prime_UTR_variant	2/2	5		ENSP00000481761

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76631 AN: 151496 Hom.: 21815 Cov.: 31

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.537

GnomAD4 exome AF: 0.602 AC: 130341 AN: 216632 Hom.: 40346 Cov.: 2 AF XY: 0.603 AC XY: 66623 AN XY: 110518

Gnomad4 AFR exome AF: 0.229

Gnomad4 AMR exome AF: 0.574

Gnomad4 ASJ exome AF: 0.690

Gnomad4 EAS exome AF: 0.672

Gnomad4 SAS exome AF: 0.592

Gnomad4 FIN exome AF: 0.681

Gnomad4 NFE exome AF: 0.601

Gnomad4 OTH exome AF: 0.583

GnomAD4 genome AF: 0.505 AC: 76627 AN: 151614 Hom.: 21800 Cov.: 31 AF XY: 0.512 AC XY: 37945 AN XY: 74092

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.663

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.537

Alfa AF: 0.535 Hom.: 4441

Bravo AF: 0.484

Asia WGS AF: 0.597 AC: 2075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10845219; hg19: chr12-10977654;