rs10492098

Positions:

• chr12-10883384-G-A
• chr12-10883384-G-C

Variant summary

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

The NM_001393989.1(PRH1):​c.65-288C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,016 control chromosomes in the GnomAD database, including 21,304 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 0.50 (21304 hom., cov: 31)
• Consequence: PRH1 NM_001393989.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.764

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRH1	NM_001393989.1	c.65-288C>T		intron_variant		ENST00000543626.5	NP_001380918.1
PRH1-PRR4	NR_037918.2	n.667-288C>T		intron_variant, non_coding_transcript_variant
PRH1	NM_001291314.2	c.65-288C>T		intron_variant			NP_001278243.1
PRH1	NM_001291315.2	c.104-288C>T		intron_variant			NP_001278244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRH1	ENST00000543626.5	c.65-288C>T		intron_variant		5	NM_001393989.1	ENSP00000479168	P1
	ENST00000703543.1	c.65-686C>T		intron_variant				ENSP00000515364	P1
PRH1	ENST00000541977.5	n.360-288C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75629 AN: 151900 Hom.: 21309 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.527

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.498 AC: 75631 AN: 152016 Hom.: 21304 Cov.: 31 AF XY: 0.507 AC XY: 37652 AN XY: 74296

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.658

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.529

Alfa AF: 0.574 Hom.: 18780

Bravo AF: 0.482

Asia WGS AF: 0.646 AC: 2243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.3
DANN	Benign	0.30

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: rs10492098; hg19: chr12-11035983;