chr6-166307775-G-C

Variant names:

• chr6-166307775-G-C
• rs772648679
• NM_175922.4:c.368C>G

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.368C>G​(p.Ser123Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000749 in 1,334,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. S123L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: PRR18 NM_175922.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52

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=0.116493195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR18	NM_175922.4	c.368C>G	p.Ser123Trp	missense_variant	Exon 1 of 1	ENST00000322583.5	NP_787118.2
LOC107986669	XR_001744464.2	n.176+52G>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR18	ENST00000322583.5	c.368C>G	p.Ser123Trp	missense_variant	Exon 1 of 1	6	NM_175922.4	ENSP00000319590.3
PRR18	ENST00000529616.1	c.*18C>G		downstream_gene_variant		2		ENSP00000433381.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.49e-7 AC: 1 AN: 1334934 Hom.: 0 Cov.: 57 AF XY: 0.00 AC XY: 0 AN XY: 661456

African (AFR) AF: 0.0000357 AC: 1 AN: 27980

American (AMR) AF: 0.00 AC: 0 AN: 32464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22306

East Asian (EAS) AF: 0.00 AC: 0 AN: 31128

South Asian (SAS) AF: 0.00 AC: 0 AN: 71568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46740

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5142

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1044038

Other (OTH) AF: 0.00 AC: 0 AN: 53568

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.87
DEOGEN2	Benign	0.057	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-2.5
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.046
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.017	D
Polyphen		0.93	P
Vest4		0.20
MutPred		0.21		Loss of glycosylation at S123 (P = 1e-04);
MVP		0.030
MPC		1.6
ClinPred		0.23	T
GERP RS		0.75
Varity_R		0.10
gMVP		0.14
Mutation Taster		=96/4	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

Publications

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Other links and lift over

dbSNP: rs772648679; hg19: chr6-166721263;