Variant chr1-116944910-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020440.4(PTGFRN):c.650G>A(p.Ser217Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000027 ( 0 hom. )

Consequence

PTGFRN
NM_020440.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06697413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGFRN	NM_020440.4 linkuse as main transcript	c.650G>A	p.Ser217Asn	missense_variant	3/9	ENST00000393203.3
PTGFRN	XM_017001874.2 linkuse as main transcript	c.668G>A	p.Ser223Asn	missense_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGFRN	ENST00000393203.3 linkuse as main transcript	c.650G>A	p.Ser217Asn	missense_variant	3/9	1	NM_020440.4	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247308

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134412

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000894

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460168

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726516

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jan 03, 2022

The c.650G>A (p.S217N) alteration is located in exon 3 (coding exon 3) of the PTGFRN gene. This alteration results from a G to A substitution at nucleotide position 650, causing the serine (S) at amino acid position 217 to be replaced by an asparagine (N). 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

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.078

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.69

M_CAP

Benign

0.0034

MetaRNN

Benign

0.067

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.3

REVEL

Benign

0.049

Sift

Benign

0.11

Sift4G

Benign

0.18

Polyphen

0.0050

Vest4

0.048

MutPred

0.32

Loss of disorder (P = 0.0785);

MVP

0.12

MPC

0.56

ClinPred

0.064

GERP RS

3.5

Varity_R

0.13

gMVP

0.28

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