Genetic Variant PRR18:p.Pro198His (chr6-166307550-G-T) – 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.593C>A(p.Pro198His) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRR18
NM_175922.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.646

Publications

0 publications found

Variant links:

Genes affected

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

PRR18 links:

LOC107986669 (HGNC:):

LOC107986669 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=0.13163054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR18	NM_175922.4 link	c.593C>A	p.Pro198His	missense_variant	Exon 1 of 1	ENST00000322583.5	NP_787118.2	Q8N4B5
LOC107986669	XR_001744464.2 link	n.3G>T		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR18	ENST00000322583.5 link	c.593C>A	p.Pro198His	missense_variant	Exon 1 of 1	6	NM_175922.4	ENSP00000319590.3		Q8N4B5
PRR18	ENST00000529616.1 link	c.*243C>A		downstream_gene_variant		2		ENSP00000433381.1		E9PL31

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1061238

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

501816

African (AFR)

AF:

0.00

AC:

AN:

21950

American (AMR)

AF:

0.00

AC:

AN:

7614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13162

East Asian (EAS)

AF:

0.00

AC:

AN:

24610

South Asian (SAS)

AF:

0.00

AC:

AN:

20180

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2864

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

907864

Other (OTH)

AF:

0.00

AC:

AN:

41994

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 29, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.593C>A (p.P198H) alteration is located in exon 1 (coding exon 1) of the PRR18 gene. This alteration results from a C to A substitution at nucleotide position 593, causing the proline (P) at amino acid position 198 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

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.023

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.21

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

0.65

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.4

REVEL

Benign

0.084

Sift

Uncertain

0.029

Sift4G

Uncertain

0.035

Polyphen

0.83

Vest4

0.12

MutPred

0.13

Loss of glycosylation at P198 (P = 0.0661);

MVP

0.13

MPC

1.1

ClinPred

0.16

GERP RS

2.4

Varity_R

0.12

gMVP

0.093

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over