chr6-166307387-C-G

Variant names:

• chr6-166307387-C-G
• rs771578999
• NM_175922.4:c.756G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_175922.4(PRR18):​c.756G>C​(p.Glu252Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,426,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PRR18 NM_175922.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 0 publications found

Genes affected

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

LOC107986669 (HGNC:):

ACMG classification

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=0.20920748).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR18	NM_175922.4	c.756G>C	p.Glu252Asp	missense_variant	Exon 1 of 1	ENST00000322583.5	NP_787118.2
LOC107986669	XR_001744464.2	n.-161C>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR18	ENST00000322583.5	c.756G>C	p.Glu252Asp	missense_variant	Exon 1 of 1	6	NM_175922.4	ENSP00000319590.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1426072 Hom.: 0 Cov.: 59 AF XY: 0.00000282 AC XY: 2 AN XY: 709638

African (AFR) AF: 0.00 AC: 0 AN: 30426

American (AMR) AF: 0.00 AC: 0 AN: 42404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25360

East Asian (EAS) AF: 0.00 AC: 0 AN: 36628

South Asian (SAS) AF: 0.00 AC: 0 AN: 83424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40662

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5648

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1102200

Other (OTH) AF: 0.0000169 AC: 1 AN: 59320

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.029
Eigen_PC	Benign	-0.047
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.036
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.87	P
Vest4		0.17
MutPred		0.21		Loss of helix (P = 0.1706);
MVP		0.092
MPC		1.3
ClinPred		0.99	D
GERP RS		0.17
Varity_R		0.68
gMVP		0.094
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs771578999; hg19: chr6-166720875;