rs2232959
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_007244.3(PRR4):c.254C>G(p.Pro85Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
PRR4
NM_007244.3 missense
NM_007244.3 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 0.0660
Publications
0 publications found
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]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07652822).
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_007244.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PRR4 | TSL:1 MANE Select | c.254C>G | p.Pro85Arg | missense | Exon 3 of 4 | ENSP00000228811.4 | Q16378-1 | ||
| PRR4 | TSL:1 | c.101-79C>G | intron | N/A | ENSP00000438046.1 | Q16378-2 | |||
| ENSG00000275778 | TSL:5 | n.*208C>G | non_coding_transcript_exon | Exon 9 of 10 | ENSP00000482961.1 | A0A087WZY1 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 152034Hom.: 0 Cov.: 30 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152034
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
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Gnomad ASJ
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Gnomad EAS
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AF:
Gnomad FIN
AF:
Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000241 AC: 6AN: 249276 AF XY: 0.0000222 show subpopulations
GnomAD2 exomes
AF:
AC:
6
AN:
249276
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461466Hom.: 0 Cov.: 34 AF XY: 0.00000688 AC XY: 5AN XY: 727028 show subpopulations
GnomAD4 exome
AF:
AC:
12
AN:
1461466
Hom.:
Cov.:
34
AF XY:
AC XY:
5
AN XY:
727028
show subpopulations
African (AFR)
AF:
AC:
2
AN:
33476
American (AMR)
AF:
AC:
1
AN:
44700
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
7
AN:
39694
South Asian (SAS)
AF:
AC:
0
AN:
86186
European-Finnish (FIN)
AF:
AC:
0
AN:
53396
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111742
Other (OTH)
AF:
AC:
1
AN:
60374
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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>80
Age
GnomAD4 genome 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74380 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152152
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
74380
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41522
American (AMR)
AF:
AC:
0
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
1
AN:
5166
South Asian (SAS)
AF:
AC:
0
AN:
4798
European-Finnish (FIN)
AF:
AC:
0
AN:
10600
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67984
Other (OTH)
AF:
AC:
0
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
4
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
PhyloP100
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
P
Vest4
MutPred
Gain of MoRF binding (P = 0.0042)
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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