5-120481255-C-A

Position:

• chr5-120481255-C-A

Variant summary

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

The ENST00000379551.2(PRR16):​c.52C>A​(p.Leu18Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRR16 ENST00000379551.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.377

Genes affected

PRR16 (HGNC:29654): (proline rich 16) Involved in positive regulation of cell size and positive regulation of translation. [provided by Alliance of Genome Resources, Apr 2022]

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=0.10516569).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRR16	NM_001300783.2	c.159+16610C>A		intron_variant		ENST00000407149.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRR16	ENST00000379551.2	c.52C>A	p.Leu18Ile	missense_variant	2/3	1
PRR16	ENST00000407149.7	c.159+16610C>A		intron_variant		1	NM_001300783.2	P1
PRR16	ENST00000509923.1	c.-52+15544C>A		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 4

GnomAD4 genome Cov.: 32

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

Dec 15, 2023

The c.52C>A (p.L18I) alteration is located in exon 2 (coding exon 1) of the PRR16 gene. This alteration results from a C to A substitution at nucleotide position 52, causing the leucine (L) at amino acid position 18 to be replaced by an isoleucine (I). 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
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.1
DANN	Benign	0.96
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.041
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.74	T
Polyphen		0.59	P
Vest4		0.16
MutPred		0.25		Gain of sheet (P = 0.0149);
MVP		0.093
MPC		0.041
ClinPred		0.66	D
GERP RS		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-119816950;