Genetic Variant GMFB:p.Gly106Arg (chr14-54479827-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_004124.3(GMFB):c.316G>A(p.Gly106Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GMFB
NM_004124.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.36

Publications

0 publications found

Variant links:

Genes affected

GMFB (HGNC:4373): (glia maturation factor beta) Predicted to enable Arp2/3 complex binding activity. Predicted to be involved in actin filament debranching and negative regulation of Arp2/3 complex-mediated actin nucleation. Predicted to act upstream of or within learning and locomotory behavior. [provided by Alliance of Genome Resources, Apr 2022]

GMFB links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.919

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004124.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMFB	NM_004124.3	MANE Select	c.316G>A	p.Gly106Arg	missense	Exon 6 of 7	NP_004115.1	P60983

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GMFB	ENST00000358056.8	TSL:1 MANE Select	c.316G>A	p.Gly106Arg	missense	Exon 6 of 7	ENSP00000350757.3	P60983
GMFB	ENST00000553333.1	TSL:3	c.355G>A	p.Gly119Arg	missense	Exon 7 of 8	ENSP00000451920.1	G3V4P8
GMFB	ENST00000554908.5	TSL:1	c.*1163G>A		3_prime_UTR	Exon 4 of 4	ENSP00000452410.1	G3V3X4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1453332

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723546

African (AFR)

AF:

0.00

AC:

AN:

33290

American (AMR)

AF:

0.00

AC:

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26016

East Asian (EAS)

AF:

0.00

AC:

AN:

39536

South Asian (SAS)

AF:

0.00

AC:

AN:

86012

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1104656

Other (OTH)

AF:

0.00

AC:

AN:

60070

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.57

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.021

MetaRNN

Pathogenic

0.92

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.4

PhyloP100

7.4

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-6.8

REVEL

Uncertain

0.63

Sift

Uncertain

0.0020

Sift4G

Benign

0.076

Polyphen

0.65

Vest4

0.91

MutPred

0.83

Gain of MoRF binding (P = 0.013)

MVP

0.63

MPC

1.4

ClinPred

0.99

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.88

gMVP

0.79

Mutation Taster

=30/70

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.22

Position offset: 32

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over