1-116910225-C-T

Position:

• chr1-116910225-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.22C>T​(p.Pro8Ser) 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. 14/21 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PTGFRN NM_020440.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.34

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=0.113345355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGFRN	NM_020440.4	c.22C>T	p.Pro8Ser	missense_variant	1/9	ENST00000393203.3	NP_065173.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGFRN	ENST00000393203.3	c.22C>T	p.Pro8Ser	missense_variant	1/9	1	NM_020440.4	ENSP00000376899.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1305332 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 638948

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.: 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

Sep 10, 2024

The c.22C>T (p.P8S) alteration is located in exon 1 (coding exon 1) of the PTGFRN gene. This alteration results from a C to T substitution at nucleotide position 22, causing the proline (P) at amino acid position 8 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	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Benign	0.70
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.0	L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	0.66	N
REVEL	Benign	0.042
Sift	Benign	0.81	T
Sift4G	Benign	0.28	T
Polyphen		0.0040	B
Vest4		0.45
MutPred		0.41		Gain of helix (P = 0.005);
MVP		0.15
MPC		0.43
ClinPred		0.075	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.041
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-117452847;