Genetic Variant PRR18:p.Thr294Arg (chr6-166307262-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_175922.4(PRR18):c.881C>G(p.Thr294Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000521 in 1,344,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000052 ( 0 hom. )

Consequence

PRR18
NM_175922.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02

Publications

1 publications found

Variant links:

Genes affected

PRR18 (HGNC:28574): (proline rich 18)

PRR18 links:

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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=0.123111874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR18	NM_175922.4 link	c.881C>G	p.Thr294Arg	missense_variant	Exon 1 of 1	ENST00000322583.5	NP_787118.2	Q8N4B5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR18	ENST00000322583.5 link	c.881C>G	p.Thr294Arg	missense_variant	Exon 1 of 1	6	NM_175922.4	ENSP00000319590.3		Q8N4B5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000206

AC:

AN:

97270

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000350

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000521

AC:

AN:

1344706

Hom.:

Cov.:

AF XY:

0.00000301

AC XY:

AN XY:

663830

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27660

American (AMR)

AF:

0.00

AC:

AN:

29840

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22818

East Asian (EAS)

AF:

0.000161

AC:

AN:

31094

South Asian (SAS)

AF:

0.00

AC:

AN:

73762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35790

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4224

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1063490

Other (OTH)

AF:

0.0000357

AC:

AN:

56028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000186

AC:

Asia WGS

AF:

0.00116

AC:

AN:

3472

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 19, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.881C>G (p.T294R) alteration is located in exon 1 (coding exon 1) of the PRR18 gene. This alteration results from a C to G substitution at nucleotide position 881, causing the threonine (T) at amino acid position 294 to be replaced by an arginine (R). 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

Uncertain

0.50

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.077

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.25

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PhyloP100

2.0

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.11

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0080

Polyphen

0.99

Vest4

0.24

MutPred

0.24

Gain of solvent accessibility (P = 0.026);

MVP

0.36

MPC

2.0

ClinPred

0.91

GERP RS

3.5

Varity_R

0.60

gMVP

0.12

Mutation Taster

=88/12

polymorphism

(source)

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

Publications

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6-166307262-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over