1-116910241-T-C

Position:

• chr1-116910241-T-C

Variant summary

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

The NM_020440.4(PTGFRN):​c.38T>C​(p.Leu13Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000307 in 1,301,980 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: PTGFRN NM_020440.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.892

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGFRN	NM_020440.4	c.38T>C	p.Leu13Pro	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.38T>C	p.Leu13Pro	missense_variant	1/9	1	NM_020440.4	ENSP00000376899.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000307 AC: 4 AN: 1301980 Hom.: 0 Cov.: 31 AF XY: 0.00000314 AC XY: 2 AN XY: 636662

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: 0.00000384

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

Dec 11, 2023

The c.38T>C (p.L13P) alteration is located in exon 1 (coding exon 1) of the PTGFRN gene. This alteration results from a T to C substitution at nucleotide position 38, causing the leucine (L) at amino acid position 13 to be replaced by a proline (P). 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	0.16
BayesDel_addAF	Benign	-0.0075	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.0027
Eigen_PC	Benign	-0.086
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.27	T
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.4	L
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.16	N
REVEL	Benign	0.22
Sift	Benign	0.25	T
Sift4G	Uncertain	0.015	D
Polyphen		0.86	P
Vest4		0.57
MutPred		0.71		Loss of helix (P = 0.0017);
MVP		0.52
MPC		0.70
ClinPred		0.58	D
GERP RS		3.4
Varity_R		0.29
gMVP		0.80

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: chr1-117452863;