6-30557379-C-A

Variant names:

• chr6-30557379-C-A
• rs375242330
• NM_025263.4:c.35C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025263.4(PRR3):​c.35C>A​(p.Pro12Gln) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P12L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRR3 NM_025263.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 0 publications found

Genes affected

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

ENSG00000308190 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057164043).

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.35C>A	p.Pro12Gln	missense	Exon 1 of 4	NP_079539.2	P79522-1
	PRR3	NM_001077497.3		c.35C>A	p.Pro12Gln	missense	Exon 1 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.35C>A	p.Pro12Gln	missense	Exon 1 of 4	ENSP00000365744.4	P79522-1
	PRR3	ENST00000376557.3	TSL:2	c.35C>A	p.Pro12Gln	missense	Exon 1 of 3	ENSP00000365740.3	P79522-2
	PRR3	ENST00000934408.1		c.35C>A	p.Pro12Gln	missense	Exon 1 of 2	ENSP00000604467.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0027	N
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.46	N
PhyloP100		-0.076
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.10
Sift	Benign	0.20	T
Sift4G	Benign	0.13	T
Polyphen		0.0010	B
Vest4		0.18
MutPred		0.15		Loss of catalytic residue at P12 (P = 0.0148)
MVP		0.13
MPC		0.32
ClinPred		0.084	T
GERP RS		-2.7
PromoterAI		-0.056	Neutral
Varity_R		0.11
gMVP		0.12
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs375242330; hg19: chr6-30525156;