4-70156061-T-C

Position:

• chr4-70156061-T-C

Variant summary

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

The NM_214711.4(PRR27):​c.59T>C​(p.Phe20Ser) 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. 12/20 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRR27 NM_214711.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33

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=0.11281714).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR27	NM_214711.4	c.59T>C	p.Phe20Ser	missense_variant	2/5	ENST00000344526.10	NP_999876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRR27	ENST00000344526.10	c.59T>C	p.Phe20Ser	missense_variant	2/5	1	NM_214711.4	ENSP00000343172.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1285170 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 642254

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Aug 21, 2024

The c.59T>C (p.F20S) alteration is located in exon 2 (coding exon 2) of the PRR27 gene. This alteration results from a T to C substitution at nucleotide position 59, causing the phenylalanine (F) at amino acid position 20 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	Pathogenic	0.66
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.073	N
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
PROVEAN	Benign	0.48	N;N
REVEL	Benign	0.050
Sift	Uncertain	0.020	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.40	B;B
Vest4		0.39
MutPred		0.49		Gain of disorder (P = 0.0048);Gain of disorder (P = 0.0048);
MVP		0.081
MPC		0.22
ClinPred		0.21	T
GERP RS		0.75
Varity_R		0.048
gMVP		0.16

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: chr4-71021778;