4-70158349-C-A

Position:

• chr4-70158349-C-A

Variant summary

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

The NM_214711.4(PRR27):​c.97C>A​(p.Pro33Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,449,924 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: PRR27 NM_214711.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.505

Genes affected

PRR27 (HGNC:33193): (proline rich 27) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

PRR27 (HGNC:):

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=0.22233817).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR27	NM_214711.4	c.97C>A	p.Pro33Thr	missense_variant	3/5	ENST00000344526.10	NP_999876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRR27	ENST00000344526.10	c.97C>A	p.Pro33Thr	missense_variant	3/5	1	NM_214711.4	ENSP00000343172.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000124 AC: 18 AN: 1449924 Hom.: 0 Cov.: 34 AF XY: 0.0000153 AC XY: 11 AN XY: 718582

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: 0.0000163

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Sep 04, 2024

The c.97C>A (p.P33T) alteration is located in exon 3 (coding exon 3) of the PRR27 gene. This alteration results from a C to A substitution at nucleotide position 97, causing the proline (P) at amino acid position 33 to be replaced by a threonine (T). 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	0.20
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T;T
Eigen	Benign	-0.072
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.63	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.81	L;L
PROVEAN	Benign	-0.83	N;N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	D;D
Vest4		0.25
MutPred		0.32		Loss of glycosylation at S37 (P = 0.0546);Loss of glycosylation at S37 (P = 0.0546);
MVP		0.31
MPC		0.035
ClinPred		0.23	T
GERP RS		3.0
Varity_R		0.13
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1015593919; hg19: chr4-71024066;