12-10825055-T-C

Variant names:

• chr12-10825055-T-C
• rs10845219
• ENST00000538332.2:c.*157A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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]

TAS2R10 (HGNC:14918): (taste 2 receptor member 10) This gene product belongs to the family of candidate taste receptors that are members of the G-protein-coupled receptor superfamily. These proteins are specifically expressed in the taste receptor cells of the tongue and palate epithelia. They are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. In functional expression studies, they respond to bitter tastants. This gene maps to the taste receptor gene cluster on chromosome 12p13. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000538332.2. 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
	TAS2R10	NM_023921.2	MANE Select	c.*291A>G		downstream_gene	N/A	NP_076410.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRH1	ENST00000538332.2	TSL:5	c.*157A>G		3_prime_UTR	Exon 2 of 2	ENSP00000481761.1
	TAS2R10	ENST00000240619.3	TSL:6 MANE Select	c.*291A>G		downstream_gene	N/A	ENSP00000240619.2

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

African (AFR) AF: 0.229 AC: 1596 AN: 6976

American (AMR) AF: 0.574 AC: 5250 AN: 9152

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 5430 AN: 7874

East Asian (EAS) AF: 0.672 AC: 12832 AN: 19098

South Asian (SAS) AF: 0.592 AC: 3557 AN: 6008

European-Finnish (FIN) AF: 0.681 AC: 9694 AN: 14242

Middle Eastern (MID) AF: 0.663 AC: 713 AN: 1076

European-Non Finnish (NFE) AF: 0.601 AC: 82904 AN: 137862

Other (OTH) AF: 0.583 AC: 8365 AN: 14344

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

African (AFR) AF: 0.227 AC: 9405 AN: 41416

American (AMR) AF: 0.568 AC: 8635 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2353 AN: 3466

East Asian (EAS) AF: 0.663 AC: 3406 AN: 5138

South Asian (SAS) AF: 0.601 AC: 2886 AN: 4804

European-Finnish (FIN) AF: 0.686 AC: 7228 AN: 10540

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40620 AN: 67746

Other (OTH) AF: 0.537 AC: 1131 AN: 2106

Alfa AF: 0.545 Hom.: 8630

Bravo AF: 0.484

Asia WGS AF: 0.597 AC: 2075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.41
PhyloP100		0.050

Splicing

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

Other links and lift over

dbSNP: rs10845219; hg19: chr12-10977654;