6-30561858-C-T

Variant names:

• chr6-30561858-C-T
• NM_025263.4:c.194C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• Publications: 0 publications found

Genes affected

PRR3 (HGNC:21149): (proline rich 3) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000290047 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09898269).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025263.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRR3	NM_025263.4	MANE Select	c.194C>T	p.Ser65Leu	missense	Exon 3 of 4	NP_079539.2	P79522-1
	PRR3	NM_001077497.3		c.131C>T	p.Ser44Leu	missense	Exon 2 of 3	NP_001070965.1	P79522-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRR3	ENST00000376560.8	TSL:1 MANE Select	c.194C>T	p.Ser65Leu	missense	Exon 3 of 4	ENSP00000365744.4	P79522-1
	PRR3	ENST00000376557.3	TSL:2	c.131C>T	p.Ser44Leu	missense	Exon 2 of 3	ENSP00000365740.3	P79522-2
	PRR3	ENST00000934408.1		c.107-531C>T		intron	N/A	ENSP00000604467.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		1.9
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.088
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.40	T
Polyphen		0.0	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
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

hg19: chr6-30529635;