Genetic Variant NM_004877.4:c.76G>A (chr19-39335459-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004877.4(GMFG):c.76G>A(p.Glu26Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E26Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

GMFG
NM_004877.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.10

Publications

0 publications found

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]

GMFG links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2950431).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004877.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GMFG	NM_004877.4	MANE Select	c.76G>A	p.Glu26Lys	missense	Exon 2 of 7	NP_004868.1	O60234
GMFG	NM_001411106.1		c.-24G>A		5_prime_UTR	Exon 2 of 7	NP_001398035.1	M0R0C1
GMFG	NM_001301008.2		c.-23-149G>A		intron	N/A	NP_001287937.1	M0R1D2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GMFG	ENST00000597595.6	TSL:1 MANE Select	c.76G>A	p.Glu26Lys	missense	Exon 2 of 7	ENSP00000472249.1	O60234
GMFG	ENST00000598034.5	TSL:1	c.76G>A	p.Glu26Lys	missense	Exon 2 of 6	ENSP00000469877.1	M0QYJ8
GMFG	ENST00000904715.1		c.76G>A	p.Glu26Lys	missense	Exon 3 of 8	ENSP00000574774.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251486

AF XY:

0.00000736

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461526

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727128

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111680

Other (OTH)

AF:

0.0000497

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.053

Eigen

Benign

0.099

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.013

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.5

PhyloP100

7.1

PrimateAI

Uncertain

0.72

Sift4G

Benign

0.47

Polyphen

0.16

Vest4

0.57

MutPred

0.50

Gain of MoRF binding (P = 0.0161)

MVP

0.37

MPC

0.25

ClinPred

0.97

GERP RS

4.2

Varity_R

0.34

gMVP

0.61

Mutation Taster

=80/20

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over