22-31712249-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173566.3(PRR14L):c.5590C>T(p.Arg1864Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1864Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: PRR14L NM_173566.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0940

Genes affected

PRR14L (HGNC:28738): (proline rich 14 like)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20025533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRR14L	NM_173566.3	c.5590C>T	p.Arg1864Trp	missense_variant	4/9	ENST00000327423.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRR14L	ENST00000327423.11	c.5590C>T	p.Arg1864Trp	missense_variant	4/9	5	NM_173566.3	P1
PRR14L	ENST00000330495.8	c.499C>T	p.Arg167Trp	missense_variant	1/6	1
PRR14L	ENST00000492705.1	n.99C>T		non_coding_transcript_exon_variant	1/2	2
PRR14L	ENST00000431684.1	c.1597C>T	p.Arg533Trp	missense_variant, NMD_transcript_variant	1/5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000239 AC: 6 AN: 251352 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135826

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000192 AC: 28 AN: 1461888 Hom.: 0 Cov.: 33 AF XY: 0.0000220 AC XY: 16 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000428

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 05, 2023

The c.5590C>T (p.R1864W) alteration is located in exon 4 (coding exon 3) of the PRR14L gene. This alteration results from a C to T substitution at nucleotide position 5590, causing the arginine (R) at amino acid position 1864 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	0.27
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	20
Dann	Uncertain	1.0
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.14	N
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.43		Loss of solvent accessibility (P = 0.0079);
MVP		0.25
MPC		0.34
ClinPred		0.84	D
GERP RS		-0.68
Varity_R		0.25
gMVP		0.53

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

LitVar

Other links and lift over

dbSNP: rs751253317; hg19: chr22-32108235; COSMIC: COSV57882730; COSMIC: COSV57882730;