19-39335292-C-T

Variant summary

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

The NM_004877.4(GMFG):​c.119G>A​(p.Arg40Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,565,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R40G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

GMFG
NM_004877.4 missense

Scores

4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47
Variant links:
Genes affected
GMFG (HGNC:4374): (glia maturation factor gamma) 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 be located in extracellular region; ficolin-1-rich granule lumen; and secretory granule lumen. [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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23385805).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GMFGNM_004877.4 linkc.119G>A p.Arg40Gln missense_variant Exon 3 of 7 ENST00000597595.6 NP_004868.1 O60234
GMFGNM_001411106.1 linkc.20G>A p.Arg7Gln missense_variant Exon 3 of 7 NP_001398035.1
GMFGNM_001301008.2 linkc.-5G>A 5_prime_UTR_variant Exon 2 of 6 NP_001287937.1 O60234M0R1D2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GMFGENST00000597595.6 linkc.119G>A p.Arg40Gln missense_variant Exon 3 of 7 1 NM_004877.4 ENSP00000472249.1 O60234

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000189
AC:
4
AN:
211998
Hom.:
0
AF XY:
0.00000894
AC XY:
1
AN XY:
111904
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:
0.0000311
Gnomad OTH exome
AF:
0.000198
GnomAD4 exome
AF:
0.0000184
AC:
26
AN:
1413620
Hom.:
0
Cov.:
30
AF XY:
0.0000143
AC XY:
10
AN XY:
697086
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000447
Gnomad4 EAS exome
AF:
0.0000254
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000203
Gnomad4 OTH exome
AF:
0.0000343
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152162
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340
ExAC
AF:
0.00000826
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.119G>A (p.R40Q) alteration is located in exon 3 (coding exon 3) of the GMFG gene. This alteration results from a G to A substitution at nucleotide position 119, causing the arginine (R) at amino acid position 40 to be replaced by a glutamine (Q). 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
0.071
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.45
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.030
T;.;T;T;.;T
Eigen
Uncertain
0.20
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Benign
0.69
D
LIST_S2
Uncertain
0.97
D;D;.;D;D;D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.23
T;T;T;T;T;T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
1.5
L;.;.;.;.;.
PrimateAI
Benign
0.44
T
REVEL
Benign
0.15
Sift4G
Benign
0.18
T;T;.;.;T;T
Polyphen
0.76
P;.;.;.;.;.
Vest4
0.33
MutPred
0.36
Loss of ubiquitination at K38 (P = 0.0806);Loss of ubiquitination at K38 (P = 0.0806);.;.;Loss of ubiquitination at K38 (P = 0.0806);Loss of ubiquitination at K38 (P = 0.0806);
MVP
0.61
MPC
0.29
ClinPred
0.57
D
GERP RS
4.8
Varity_R
0.57
gMVP
0.21

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.

Other links and lift over

dbSNP: rs753677461; hg19: chr19-39825932; API