1-116944712-C-T

Position:

• chr1-116944712-C-T

Variant summary

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

The NM_020440.4(PTGFRN):​c.452C>T​(p.Ala151Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 1,261,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: PTGFRN NM_020440.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.304

Genes affected

PTGFRN (HGNC:9601): (prostaglandin F2 receptor inhibitor) Predicted to be involved in myoblast fusion involved in skeletal muscle regeneration. Predicted to act upstream of or within lipid droplet organization. Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

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=0.10076642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGFRN	NM_020440.4	c.452C>T	p.Ala151Val	missense_variant	3/9	ENST00000393203.3
PTGFRN	XM_017001874.2	c.470C>T	p.Ala157Val	missense_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGFRN	ENST00000393203.3	c.452C>T	p.Ala151Val	missense_variant	3/9	1	NM_020440.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000159 AC: 2 AN: 1261192 Hom.: 0 Cov.: 31 AF XY: 0.00000163 AC XY: 1 AN XY: 615218

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: 9.78e-7

Gnomad4 OTH exome AF: 0.0000194

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Mar 28, 2024

The c.452C>T (p.A151V) alteration is located in exon 3 (coding exon 3) of the PTGFRN gene. This alteration results from a C to T substitution at nucleotide position 452, causing the alanine (A) at amino acid position 151 to be replaced by a valine (V). 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	0.076
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.058
Sift	Benign	0.14	T
Sift4G	Benign	0.10	T
Polyphen		0.90	P
Vest4		0.060
MutPred		0.15		Loss of relative solvent accessibility (P = 0.0404);
MVP		0.15
MPC		0.43
ClinPred		0.24	T
GERP RS		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.036
gMVP		0.47

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: rs1437010284; hg19: chr1-117487334;