chr6-30561858-C-T

Position:

• chr6-30561858-C-T

Variant summary

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

The NM_025263.4(PRR3):​c.194C>T​(p.Ser65Leu) 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. 14/21 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: PRR3 NM_025263.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.88

Genes affected

PRR3 (HGNC:21149): (proline rich 3) Enables RNA binding activity. [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=0.09898269).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRR3	NM_025263.4	c.194C>T	p.Ser65Leu	missense_variant	3/4	ENST00000376560.8
PRR3	NM_001077497.3	c.131C>T	p.Ser44Leu	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRR3	ENST00000376560.8	c.194C>T	p.Ser65Leu	missense_variant	3/4	1	NM_025263.4	P2

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

Jul 05, 2023

The c.194C>T (p.S65L) alteration is located in exon 3 (coding exon 3) of the PRR3 gene. This alteration results from a C to T substitution at nucleotide position 194, causing the serine (S) at amino acid position 65 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	0.14
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	0.025
FATHMM_MKL	Benign	0.70	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.099	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;.
MutationTaster	Benign	0.96	N;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.088
Sift	Uncertain	0.0010	D;D
Sift4G	Benign	0.40	T;T
Polyphen		0.0	B;B
Vest4		0.21
MutPred		0.10		Loss of phosphorylation at S65 (P = 0.0042);.;
MVP		0.41
MPC		0.33
ClinPred		0.61	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr6-30529635;