NM_015026.3:c.124G>A

Variant names:

• chr12-62484182-G-A
• NM_015026.3:c.124G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015026.3(MON2):​c.124G>A​(p.Gly42Arg) 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: 33)
• Consequence: MON2 NM_015026.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.41
• Publications: 0 publications found

Genes affected

MON2 (HGNC:29177): (MON2 homolog, regulator of endosome-to-Golgi trafficking) Predicted to be involved in Golgi to endosome transport. Located in early endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

MON2-AS1 (HGNC:56698): (MON2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.799

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015026.3. 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
	MON2	NM_015026.3	MANE Select	c.124G>A	p.Gly42Arg	missense	Exon 2 of 35	NP_055841.2	Q7Z3U7-1
	MON2	NM_001278470.2		c.124G>A	p.Gly42Arg	missense	Exon 2 of 34	NP_001265399.1	Q7Z3U7-5
	MON2	NM_001278471.2		c.124G>A	p.Gly42Arg	missense	Exon 2 of 34	NP_001265400.1	Q7Z3U7-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MON2	ENST00000393630.8	TSL:1 MANE Select	c.124G>A	p.Gly42Arg	missense	Exon 2 of 35	ENSP00000377250.4	Q7Z3U7-1
	MON2	ENST00000393629.6	TSL:1	c.124G>A	p.Gly42Arg	missense	Exon 2 of 34	ENSP00000377249.2	Q7Z3U7-5
	MON2	ENST00000552738.5	TSL:1	c.124G>A	p.Gly42Arg	missense	Exon 2 of 34	ENSP00000449215.1	Q7Z3U7-6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.19	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.045	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.8	L
PhyloP100		9.4
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.010	D
Vest4		0.91
MutPred		0.51		Gain of MoRF binding (P = 0.0227)
MVP		0.58
ClinPred		0.98	D
GERP RS		6.1
Varity_R		0.59
gMVP		0.90
Mutation Taster		=39/61	disease causing

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

Other links and lift over

hg19: chr12-62877962;