NM_175922.4:c.844C>G

Variant names:

• chr6-166307299-G-C
• rs765749360
• NM_175922.4:c.844C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_175922.4(PRR18):​c.844C>G​(p.Arg282Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,382,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. R282W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRR18 NM_175922.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.491
• Publications: 0 publications found

Genes affected

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

LOC107986669 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27121884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR18	NM_175922.4	c.844C>G	p.Arg282Gly	missense_variant	Exon 1 of 1	ENST00000322583.5	NP_787118.2
LOC107986669	XR_001744464.2	n.-249G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR18	ENST00000322583.5	c.844C>G	p.Arg282Gly	missense_variant	Exon 1 of 1	6	NM_175922.4	ENSP00000319590.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1382686 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 684626

African (AFR) AF: 0.00 AC: 0 AN: 29124

American (AMR) AF: 0.00 AC: 0 AN: 35912

Ashkenazi Jewish (ASJ) AF: 0.0000409 AC: 1 AN: 24462

East Asian (EAS) AF: 0.00 AC: 0 AN: 33918

South Asian (SAS) AF: 0.00 AC: 0 AN: 78928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4958

European-Non Finnish (NFE) AF: 9.25e-7 AC: 1 AN: 1081200

Other (OTH) AF: 0.00 AC: 0 AN: 57654

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.38	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.49
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.092
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.12	T
Polyphen		0.97	D
Vest4		0.21
MutPred		0.33		Loss of methylation at R282 (P = 0.0032);
MVP		0.17
MPC		1.7
ClinPred		0.78	D
GERP RS		2.5
Varity_R		0.40
gMVP		0.058
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs765749360; hg19: chr6-166720787;