Variant rs769997784 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004864.4(GDF15):c.560A>C(p.Gln187Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000415 in 1,446,542 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

GDF15
NM_004864.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.81

Variant links:

Genes affected

GDF15 (HGNC:30142): (growth differentiation factor 15) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. The protein is expressed in a broad range of cell types, acts as a pleiotropic cytokine and is involved in the stress response program of cells after cellular injury. Increased protein levels are associated with disease states such as tissue hypoxia, inflammation, acute injury and oxidative stress. [provided by RefSeq, Aug 2016]

GDF15 links:

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ACMG classification

Classification made for transcript

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=0.07467151).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDF15	NM_004864.4 link	c.560A>C	p.Gln187Pro	missense_variant	Exon 2 of 2	ENST00000252809.3	NP_004855.2	Q99988

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GDF15	ENST00000252809.3 link	c.560A>C	p.Gln187Pro	missense_variant	Exon 2 of 2	1	NM_004864.4	ENSP00000252809.3	Q99988
GDF15	ENST00000595973.3 link	c.560A>C	p.Gln187Pro	missense_variant	Exon 3 of 3	5		ENSP00000470531.3	Q99988A0A0A0MTT8
GDF15	ENST00000597765.2 link	c.560A>C	p.Gln187Pro	missense_variant	Exon 3 of 3	4		ENSP00000469819.2	Q99988
GDF15	ENST00000594925.1 link	n.*84A>C		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000415

AC:

AN:

1446542

Hom.:

Cov.:

AF XY:

0.00000834

AC XY:

AN XY:

719466

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:

0.00000451

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.0

DANN

Benign

0.56

DEOGEN2

Benign

0.13

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0080

LIST_S2

Benign

0.31

M_CAP

Uncertain

0.098

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.4

REVEL

Benign

0.14

Sift

Benign

0.18

Sift4G

Benign

0.31

Polyphen

0.0

Vest4

0.049

MutPred

0.30

Gain of glycosylation at Q187 (P = 0.0105);

MVP

0.33

MPC

0.77

ClinPred

0.029

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.74

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over