NM_175922.4:c.571C>T

Variant names:

• chr6-166307572-G-A
• rs935745794
• NM_175922.4:c.571C>T

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.571C>T​(p.Pro191Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000937 in 1,066,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. P191T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: PRR18 NM_175922.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363
• 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=0.11420515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR18	NM_175922.4	c.571C>T	p.Pro191Ser	missense_variant	Exon 1 of 1	ENST00000322583.5	NP_787118.2
LOC107986669	XR_001744464.2	n.25G>A		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	c.571C>T	p.Pro191Ser	missense_variant	Exon 1 of 1	6	NM_175922.4	ENSP00000319590.3
PRR18	ENST00000529616.1	c.*221C>T		downstream_gene_variant		2		ENSP00000433381.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.37e-7 AC: 1 AN: 1066758 Hom.: 0 Cov.: 60 AF XY: 0.00000198 AC XY: 1 AN XY: 504900

African (AFR) AF: 0.00 AC: 0 AN: 22068

American (AMR) AF: 0.00 AC: 0 AN: 7768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13318

East Asian (EAS) AF: 0.00 AC: 0 AN: 25236

South Asian (SAS) AF: 0.00 AC: 0 AN: 20872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2902

European-Non Finnish (NFE) AF: 0.00000110 AC: 1 AN: 910684

Other (OTH) AF: 0.00 AC: 0 AN: 42292

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	10
DANN	Benign	0.97
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.36
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.021
Sift	Benign	0.039	D
Sift4G	Benign	0.073	T
Polyphen		0.50	P
Vest4		0.062
MutPred		0.24		Gain of phosphorylation at P191 (P = 0.002);
MVP		0.014
MPC		1.9
ClinPred		0.65	D
GERP RS		-4.4
Varity_R		0.038
gMVP		0.10
Mutation Taster		=98/2	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: rs935745794; hg19: chr6-166721060;