3-139005742-G-C

Variant summary

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

The NM_001134659.1(PRR23A):c.527C>G(p.Ala176Gly) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PRR23A NM_001134659.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.05

Genes affected

PRR23A (HGNC:37172): (proline rich 23A)

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=0.08359331).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRR23A	NM_001134659.1	c.527C>G	p.Ala176Gly	missense_variant	1/1	ENST00000383163.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRR23A	ENST00000383163.4	c.527C>G	p.Ala176Gly	missense_variant	1/1		NM_001134659.1	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247714 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134680

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 31

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

Nov 02, 2023

The c.527C>G (p.A176G) alteration is located in exon 1 (coding exon 1) of the PRR23A gene. This alteration results from a C to G substitution at nucleotide position 527, causing the alanine (A) at amino acid position 176 to be replaced by a glycine (G). 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	0.16
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	7.7
Dann	Benign	0.93
DEOGEN2	Benign	0.088	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0075	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.025
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.028	B
Vest4		0.10
MutPred		0.47		Gain of relative solvent accessibility (P = 0.0082);
MVP		0.030
MPC		1.1
ClinPred		0.14	T
GERP RS		-5.8
Varity_R		0.22
gMVP		0.083

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

LitVar

Other links and lift over

dbSNP: rs1240750358; hg19: chr3-138724584;