6-30558183-C-G

Variant names:

• chr6-30558183-C-G
• NM_025263.4:c.140C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_025263.4(PRR3):​c.140C>G​(p.Ala47Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 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: 3.27
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.140C>G	p.Ala47Gly	missense	Exon 2 of 4	NP_079539.2	P79522-1
	PRR3	NM_001077497.3		c.106+733C>G		intron	N/A	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.140C>G	p.Ala47Gly	missense	Exon 2 of 4	ENSP00000365744.4	P79522-1
	PRR3	ENST00000376557.3	TSL:2	c.106+733C>G		intron	N/A	ENSP00000365740.3	P79522-2
	PRR3	ENST00000934408.1		c.106+733C>G		intron	N/A	ENSP00000604467.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.18
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.76	D
M_CAP	Benign	0.0064	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		3.3
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.063
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.19	T
Polyphen		0.70	P
Vest4		0.58
MutPred		0.12		Loss of stability (P = 0.1114)
MVP		0.62
MPC		0.44
ClinPred		0.59	D
GERP RS		4.9
Varity_R		0.15
gMVP		0.12
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr6-30525960;