rs772648679

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-166307775-G-A
• chr6-166307775-G-C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_175922.4(PRR18):​c.368C>T​(p.Ser123Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000787 in 1,485,856 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000084 (2 hom.)
• Consequence: PRR18 NM_175922.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.52

Genes affected

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

LOC107986669 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032978117).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR18	NM_175922.4	c.368C>T	p.Ser123Leu	missense_variant	Exon 1 of 1	ENST00000322583.5	NP_787118.2
LOC107986669	XR_001744464.2	n.176+52G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR18	ENST00000322583.5	c.368C>T	p.Ser123Leu	missense_variant	Exon 1 of 1	6	NM_175922.4	ENSP00000319590.3
PRR18	ENST00000529616.1	c.*18C>T		downstream_gene_variant		2		ENSP00000433381.1

Frequencies

GnomAD3 genomes AF: 0.0000332 AC: 5 AN: 150814 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000444

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000137 AC: 2 AN: 146024 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000122

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000156

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000839 AC: 112 AN: 1334934 Hom.: 2 Cov.: 57 AF XY: 0.0000771 AC XY: 51 AN XY: 661456

African (AFR) AF: 0.00 AC: 0 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: 0.00238 AC: 74 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: 0.0000345 AC: 36 AN: 1044038

Other (OTH) AF: 0.0000373 AC: 2 AN: 53568

GnomAD4 genome AF: 0.0000331 AC: 5 AN: 150922 Hom.: 0 Cov.: 32 AF XY: 0.0000542 AC XY: 4 AN XY: 73738

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000444 AC: 3 AN: 67496

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000380 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000173 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.368C>T (p.S123L) 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 368, causing the serine (S) at amino acid position 123 to be replaced by a leucine (L). 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	0.16
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.1
DANN	Benign	0.79
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.5
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.025
Sift	Benign	0.25	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.054
MutPred		0.18		Loss of glycosylation at S123 (P = 1e-04);
MVP		0.014
MPC		0.83
ClinPred		0.96	D
GERP RS		0.75
Varity_R		0.034
gMVP		0.13
Mutation Taster		=97/3	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;