Variant 1-116942077-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020440.4(PTGFRN):c.412G>T(p.Val138Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,264 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 1 hom. )

Consequence

PTGFRN
NM_020440.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.23

Variant links:

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]

PTGFRN links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.412G>T	p.Val138Phe	missense_variant	2/9	ENST00000393203.3	NP_065173.2	Q9P2B2
PTGFRN	XM_017001874.2 linkuse as main transcript	c.430G>T	p.Val144Phe	missense_variant	2/9		XP_016857363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGFRN	ENST00000393203.3 linkuse as main transcript	c.412G>T	p.Val138Phe	missense_variant	2/9	1	NM_020440.4	ENSP00000376899.2		Q9P2B2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249792

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134878

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1459264

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725446

show subpopulations

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:

0.0000581

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.412G>T (p.V138F) alteration is located in exon 2 (coding exon 2) of the PTGFRN gene. This alteration results from a G to T substitution at nucleotide position 412, causing the valine (V) at amino acid position 138 to be replaced by a phenylalanine (F). 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

0.76

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.78

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.68

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.8

REVEL

Benign

0.17

Sift

Uncertain

0.017

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.69

MutPred

0.64

Gain of sheet (P = 0.0149);

MVP

0.23

MPC

1.5

ClinPred

0.80

GERP RS

4.2

Varity_R

0.21

gMVP

0.84

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over