2-27137476-T-C

Variant names:

• chr2-27137476-T-C
• NM_178553.4:c.854A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178553.4(PRR30):​c.854A>G​(p.Gln285Arg) 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. 15/21 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: PRR30 NM_178553.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.109
• Publications: 0 publications found

Genes affected

PRR30 (HGNC:28677): (proline rich 30)

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=0.07499692).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178553.4. 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
	PRR30	NM_178553.4	MANE Select	c.854A>G	p.Gln285Arg	missense	Exon 3 of 3	NP_848648.2	Q53SZ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRR30	ENST00000335524.7	TSL:1 MANE Select	c.854A>G	p.Gln285Arg	missense	Exon 3 of 3	ENSP00000335017.3	Q53SZ7
	PRR30	ENST00000432962.2	TSL:3	c.360A>G	p.Ala120Ala	synonymous	Exon 4 of 4	ENSP00000393468.2	C9JVA3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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	0.092
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.3
DANN	Benign	0.93
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.11
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.0070
Sift	Benign	0.17	T
Sift4G	Benign	0.13	T
Polyphen		0.0030	B
Vest4		0.16
MutPred		0.28		Gain of solvent accessibility (P = 0.0171)
MVP		0.20
MPC		0.31
ClinPred		0.047	T
GERP RS		0.73
Varity_R		0.11
gMVP		0.48
Mutation Taster		=100/0	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

hg19: chr2-27360344;