NM_007244.3:c.287G>C

Variant names:

• chr12-10847181-C-G
• rs1063193
• NM_007244.3:c.287G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007244.3(PRR4):​c.287G>C​(p.Arg96Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R96Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRR4 NM_007244.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.34

Genes affected

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]

ENSG00000275778 (HGNC:):

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03399372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR4	NM_007244.3	c.287G>C	p.Arg96Pro	missense_variant	Exon 3 of 4	ENST00000228811.8	NP_009175.2
PRR4	NM_001098538.3	c.101-46G>C		intron_variant	Intron 2 of 3		NP_001092008.2
PRH1-PRR4	NR_037918.2	n.1407G>C		non_coding_transcript_exon_variant	Exon 9 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR4	ENST00000228811.8	c.287G>C	p.Arg96Pro	missense_variant	Exon 3 of 4	1	NM_007244.3	ENSP00000228811.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1461542 Hom.: 0 Cov.: 69 AF XY: 0.00 AC XY: 0 AN XY: 727046

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.29
DANN	Benign	0.66
DEOGEN2	Benign	0.0023	T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.00021	N
LIST_S2	Benign	0.34	.;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.034	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.0	N;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.67	N;.
REVEL	Benign	0.017
Sift	Benign	0.062	T;.
Sift4G	Benign	0.39	T;T
Polyphen		0.0010	B;.
Vest4		0.082
MutPred		0.22		Loss of MoRF binding (P = 0.0029);.;
MVP		0.030
MPC		0.16
ClinPred		0.088	T
GERP RS		-3.5
Varity_R		0.12
gMVP		0.023

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1063193; hg19: chr12-10999780;