rs765749360

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-166307299-G-A
• chr6-166307299-G-C
• chr6-166307299-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_175922.4(PRR18):​c.844C>T​(p.Arg282Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 1,534,776 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: PRR18 NM_175922.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.491
• Publications: 0 publications found

Genes affected

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

LOC107986669 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2075293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR18	NM_175922.4	c.844C>T	p.Arg282Trp	missense_variant	Exon 1 of 1	ENST00000322583.5	NP_787118.2
LOC107986669	XR_001744464.2	n.-249G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR18	ENST00000322583.5	c.844C>T	p.Arg282Trp	missense_variant	Exon 1 of 1	6	NM_175922.4	ENSP00000319590.3

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152092 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000124 AC: 17 AN: 137106 AF XY: 0.0000775

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000155

Gnomad OTH exome AF: 0.000268

GnomAD4 exome AF: 0.000192 AC: 265 AN: 1382684 Hom.: 0 Cov.: 30 AF XY: 0.000190 AC XY: 130 AN XY: 684626

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

American (AMR) AF: 0.000167 AC: 6 AN: 35912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24462

East Asian (EAS) AF: 0.00 AC: 0 AN: 33916

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

European-Finnish (FIN) AF: 0.0000821 AC: 3 AN: 36530

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

European-Non Finnish (NFE) AF: 0.000228 AC: 247 AN: 1081200

Other (OTH) AF: 0.000156 AC: 9 AN: 57654

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152092 Hom.: 0 Cov.: 34 AF XY: 0.0000808 AC XY: 6 AN XY: 74288

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000175 Hom.: 0

Bravo AF: 0.0000831

ExAC AF: 0.0000619 AC: 7

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.844C>T (p.R282W) alteration is located in exon 1 (coding exon 1) of the PRR18 gene. This alteration results from a C to T substitution at nucleotide position 844, causing the arginine (R) at amino acid position 282 to be replaced by a tryptophan (W). 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	0.23
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.49
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.11
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.23
MutPred		0.37		Loss of disorder (P = 9e-04);
MVP		0.24
MPC		1.9
ClinPred		0.30	T
GERP RS		2.5
Varity_R		0.28
gMVP		0.058
Mutation Taster		=94/6	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;