NM_001393989.1:c.65-288C>T

Variant names:

• chr12-10883384-G-A
• rs10492098
• NM_001393989.1:c.65-288C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

ENSG00000275778 (HGNC:):

PRR4 (HGNC:18020): (proline rich 4) This gene encodes a member of the proline-rich protein family that lacks a conserved repetitive domain. This protein may play a role in protective functions in the eye. Alternative splicing result in multiple transcript variants. Read-through transcription also exists between this gene and the upstream PRH1 (proline-rich protein HaeIII subfamily 1) gene. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393989.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRH1	NM_001393989.1	MANE Select	c.65-288C>T		intron	N/A	NP_001380918.1
	PRH1	NM_001291315.2		c.104-288C>T		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.65-288C>T		intron	N/A	NP_001278243.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRH1	ENST00000543626.5	TSL:5 MANE Select	c.65-288C>T		intron	N/A	ENSP00000479168.1
	ENSG00000275778	ENST00000536668.2	TSL:5	n.299-288C>T		intron	N/A	ENSP00000482961.1
	PRH1	ENST00000703543.1		c.65-686C>T		intron	N/A	ENSP00000515364.1

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

African (AFR) AF: 0.219 AC: 9060 AN: 41420

American (AMR) AF: 0.595 AC: 9096 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2216 AN: 3472

East Asian (EAS) AF: 0.729 AC: 3765 AN: 5168

South Asian (SAS) AF: 0.656 AC: 3160 AN: 4820

European-Finnish (FIN) AF: 0.658 AC: 6950 AN: 10566

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39374 AN: 67962

Other (OTH) AF: 0.529 AC: 1117 AN: 2112

Alfa AF: 0.533 Hom.: 27197

Bravo AF: 0.482

Asia WGS AF: 0.646 AC: 2243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.3
DANN	Benign	0.30
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10492098; hg19: chr12-11035983;