2-27137188-G-T

Variant summary

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

The NM_178553.4(PRR30):c.1142C>A(p.Ala381Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRR30 NM_178553.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.506

Genes affected

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

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=0.079616904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRR30	NM_178553.4	c.1142C>A	p.Ala381Glu	missense_variant	3/3	ENST00000335524.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRR30	ENST00000335524.7	c.1142C>A	p.Ala381Glu	missense_variant	3/3	1	NM_178553.4	P1
PRR30	ENST00000432962.2	c.648C>A	p.Gly216=	synonymous_variant	4/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461884 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000611 Hom.: 0

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

Oct 27, 2023

The c.1142C>A (p.A381E) alteration is located in exon 3 (coding exon 1) of the PRR30 gene. This alteration results from a C to A substitution at nucleotide position 1142, causing the alanine (A) at amino acid position 381 to be replaced by a glutamic acid (E). 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	-0.28	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	12
Dann	Benign	0.86
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.042
Sift	Benign	0.29	T
Sift4G	Benign	0.19	T
Polyphen		0.34	B
Vest4		0.17
MutPred		0.072		Gain of ubiquitination at K383 (P = 0.0683);
MVP		0.13
MPC		0.54
ClinPred		0.11	T
GERP RS		1.7
Varity_R		0.11
gMVP		0.11

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-27360056;