chr14-54479827-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

10
5
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.36
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.919

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GMFBNM_004124.3 linkc.316G>A p.Gly106Arg missense_variant Exon 6 of 7 ENST00000358056.8 NP_004115.1 P60983

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GMFBENST00000358056.8 linkc.316G>A p.Gly106Arg missense_variant Exon 6 of 7 1 NM_004124.3 ENSP00000350757.3 P60983
GMFBENST00000553333.1 linkc.355G>A p.Gly119Arg missense_variant Exon 7 of 8 3 ENSP00000451920.1 G3V4P8
GMFBENST00000554908.5 linkc.*1163G>A 3_prime_UTR_variant Exon 4 of 4 1 ENSP00000452410.1 G3V3X4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1453332
Hom.:
0
Cov.:
26
AF XY:
0.00
AC XY:
0
AN XY:
723546
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 19, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.316G>A (p.G106R) alteration is located in exon 6 (coding exon 6) of the GMFB gene. This alteration results from a G to A substitution at nucleotide position 316, causing the glycine (G) at amino acid position 106 to be replaced by an arginine (R). 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
1.0
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.57
D;D;.
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
.;D;D
M_CAP
Benign
0.021
T
MetaRNN
Pathogenic
0.92
D;D;D
MetaSVM
Benign
-0.51
T
MutationAssessor
Uncertain
2.4
M;M;.
PrimateAI
Pathogenic
0.90
D
PROVEAN
Pathogenic
-6.8
D;.;D
REVEL
Uncertain
0.63
Sift
Uncertain
0.0020
D;.;D
Sift4G
Benign
0.076
T;T;T
Polyphen
0.65
P;P;.
Vest4
0.91
MutPred
0.83
Gain of MoRF binding (P = 0.013);Gain of MoRF binding (P = 0.013);.;
MVP
0.63
MPC
1.4
ClinPred
0.99
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.88
gMVP
0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-54946545; API