4-70158754-C-T

Position:

• chr4-70158754-C-T

Variant summary

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

The NM_214711.4(PRR27):​c.502C>T​(p.Pro168Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRR27 NM_214711.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.327

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=0.12774816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR27	NM_214711.4	c.502C>T	p.Pro168Ser	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.502C>T	p.Pro168Ser	missense_variant	3/5	1	NM_214711.4	ENSP00000343172.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

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

Jun 26, 2024

The c.502C>T (p.P168S) alteration is located in exon 3 (coding exon 3) of the PRR27 gene. This alteration results from a C to T substitution at nucleotide position 502, causing the proline (P) at amino acid position 168 to be replaced by a serine (S). 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	0.21
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.5
DANN	Benign	0.47
DEOGEN2	Benign	0.057	T;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.0093	N
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L
PROVEAN	Pathogenic	-7.0	D;D
REVEL	Benign	0.027
Sift	Uncertain	0.014	D;D
Sift4G	Uncertain	0.024	D;D
Polyphen		0.78	P;P
Vest4		0.14
MutPred		0.30		Gain of helix (P = 0.005);Gain of helix (P = 0.005);
MVP		0.12
MPC		0.030
ClinPred		0.66	D
GERP RS		-2.1
Varity_R		0.18
gMVP		0.20

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: chr4-71024471;