Menu
GeneBe

11-36451302-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001160167.2(PRR5L):c.679G>C(p.Asp227His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PRR5L
NM_001160167.2 missense

Scores

10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.67
Variant links:
Genes affected
PRR5L (HGNC:25878): (proline rich 5 like) Enables ubiquitin protein ligase binding activity. Involved in several processes, including TORC2 signaling; positive regulation of mRNA catabolic process; and regulation of fibroblast migration. Part of TORC2 complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRR5LNM_001160167.2 linkuse as main transcriptc.679G>C p.Asp227His missense_variant 8/9 ENST00000530639.6
PRR5LNM_024841.5 linkuse as main transcriptc.679G>C p.Asp227His missense_variant 9/10
PRR5LNM_001160168.2 linkuse as main transcriptc.295G>C p.Asp99His missense_variant 5/6
PRR5LNM_001160169.1 linkuse as main transcriptc.585+4862G>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRR5LENST00000530639.6 linkuse as main transcriptc.679G>C p.Asp227His missense_variant 8/92 NM_001160167.2 P1Q6MZQ0-1
PRR5LENST00000378867.7 linkuse as main transcriptc.679G>C p.Asp227His missense_variant 9/101 P1Q6MZQ0-1
PRR5LENST00000527487.1 linkuse as main transcriptc.585+4862G>C intron_variant 3 Q6MZQ0-4
PRR5LENST00000389693.3 linkuse as main transcriptn.414G>C non_coding_transcript_exon_variant 5/62

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251464
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461880
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 27, 2023The c.679G>C (p.D227H) alteration is located in exon 8 (coding exon 7) of the PRR5L gene. This alteration results from a G to C substitution at nucleotide position 679, causing the aspartic acid (D) at amino acid position 227 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
0.030
Cadd
Uncertain
24
Dann
Uncertain
0.99
DEOGEN2
Benign
0.0053
T;T
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Uncertain
0.96
D
M_CAP
Uncertain
0.12
D
MetaRNN
Uncertain
0.61
D;D
MetaSVM
Uncertain
0.31
D
MutationAssessor
Benign
2.0
M;M
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.80
N;N
REVEL
Uncertain
0.52
Sift
Benign
0.18
T;T
Sift4G
Benign
0.12
T;T
Polyphen
0.99
D;D
Vest4
0.59
MutPred
0.22
Gain of MoRF binding (P = 0.0522);Gain of MoRF binding (P = 0.0522);
MVP
0.63
MPC
1.0
ClinPred
0.73
D
GERP RS
4.2
Varity_R
0.11
gMVP
0.47

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1430555922; hg19: chr11-36472852; API