5-120686491-T-G

Position:

• chr5-120686491-T-G

Variant summary

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

The NM_001300783.2(PRR16):​c.697T>G​(p.Leu233Val) 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRR16 NM_001300783.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.592

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=0.11298534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR16	NM_001300783.2	c.697T>G	p.Leu233Val	missense_variant	2/2	ENST00000407149.7	NP_001287712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRR16	ENST00000407149.7	c.697T>G	p.Leu233Val	missense_variant	2/2	1	NM_001300783.2	ENSP00000385118.2
PRR16	ENST00000379551.2	c.628T>G	p.Leu210Val	missense_variant	3/3	1		ENSP00000368869.2
PRR16	ENST00000446965.2	c.538T>G	p.Leu180Val	missense_variant	3/3	1		ENSP00000405491.2
PRR16	ENST00000505123.5	c.487T>G	p.Leu163Val	missense_variant	4/4	3		ENSP00000423446.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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 10, 2024

The c.628T>G (p.L210V) alteration is located in exon 3 (coding exon 2) of the PRR16 gene. This alteration results from a T to G substitution at nucleotide position 628, causing the leucine (L) at amino acid position 210 to be replaced by a valine (V). 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	0.080
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.81
DEOGEN2	Benign	0.013	T;.;.;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.85	D;D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.1	N;D;D;.
REVEL	Benign	0.054
Sift	Benign	0.062	T;D;D;.
Sift4G	Benign	0.95	T;T;T;T
Polyphen		0.14	B;B;.;.
Vest4		0.32
MutPred		0.17		Loss of catalytic residue at L233 (P = 0.0341);.;.;.;
MVP		0.39
MPC		0.047
ClinPred		0.27	T
GERP RS		-3.4
Varity_R		0.070
gMVP		0.23

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: chr5-120022186;