Variant 12-55748769-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_005811.5(GDF11):c.629G>T(p.Gly210Val) variant causes a missense change. The variant allele was found at a frequency of 0.00384 in 1,614,240 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 13 hom. )

Consequence

GDF11
NM_005811.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.56

Variant links:

Genes affected

GDF11 (HGNC:4216): (growth differentiation factor 11) 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. This protein plays a role in the development of the nervous and other organ systems, and may regulate aging. [provided by RefSeq, Aug 2016]

GDF11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011054188).

BP6

Variant 12-55748769-G-T is Benign according to our data. Variant chr12-55748769-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3044452.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 390 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDF11	NM_005811.5 linkuse as main transcript	c.629G>T	p.Gly210Val	missense_variant	2/3	ENST00000257868.10	NP_005802.1	O95390A0A024RB20
GDF11	XM_006719194.4 linkuse as main transcript	c.629G>T	p.Gly210Val	missense_variant	2/4		XP_006719257.1	O95390A0A024RB20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDF11	ENST00000257868.10 linkuse as main transcript	c.629G>T	p.Gly210Val	missense_variant	2/3	1	NM_005811.5	ENSP00000257868.5		O95390
GDF11	ENST00000546799.1 linkuse as main transcript	c.545G>T	p.Gly182Val	missense_variant	2/4	1		ENSP00000448390.1		H0YI30

Frequencies

GnomAD3 genomes

AF:

0.00257

AC:

391

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000747

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00435

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00215

AC:

539

AN:

251154

Hom.:

AF XY:

0.00209

AC XY:

284

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00393

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00397

AC:

5810

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00376

AC XY:

2732

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00487

Gnomad4 OTH exome

AF:

0.00414

GnomAD4 genome

AF:

0.00256

AC:

390

AN:

152382

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

173

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.000745

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00435

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00379

Hom.:

Bravo

AF:

0.00263

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00349

AC:

ExAC

AF:

0.00190

AC:

231

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00458

EpiControl

AF:

0.00474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GDF11-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 16, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.80

M_CAP

Benign

0.029

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.42

REVEL

Uncertain

0.31

Sift

Benign

0.24

Sift4G

Benign

0.18

Polyphen

1.0

Vest4

0.51

MVP

0.71

MPC

1.4

ClinPred

0.077

GERP RS

3.8

Varity_R

0.12

gMVP

0.50

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