NM_015026.3:c.611G>A

Variant names:

• chr12-62500828-G-A
• NM_015026.3:c.611G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015026.3(MON2):​c.611G>A​(p.Arg204Lys) 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 benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MON2 NM_015026.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.19
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25119823).

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.611G>A	p.Arg204Lys	missense	Exon 6 of 35	NP_055841.2	Q7Z3U7-1
	MON2	NM_001278470.2		c.611G>A	p.Arg204Lys	missense	Exon 6 of 34	NP_001265399.1	Q7Z3U7-5
	MON2	NM_001278471.2		c.611G>A	p.Arg204Lys	missense	Exon 6 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.611G>A	p.Arg204Lys	missense	Exon 6 of 35	ENSP00000377250.4	Q7Z3U7-1
	MON2	ENST00000393629.6	TSL:1	c.611G>A	p.Arg204Lys	missense	Exon 6 of 34	ENSP00000377249.2	Q7Z3U7-5
	MON2	ENST00000552738.5	TSL:1	c.611G>A	p.Arg204Lys	missense	Exon 6 of 34	ENSP00000449215.1	Q7Z3U7-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

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	Benign	0.14
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Benign	0.78
DEOGEN2	Benign	0.0095	T
Eigen	Benign	0.073
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		8.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.088
Sift	Benign	1.0	T
Sift4G	Benign	0.45	T
Polyphen		0.015	B
Vest4		0.23
MutPred		0.37		Loss of stability (P = 0.0188)
MVP		0.19
ClinPred		0.81	D
GERP RS		5.2
Varity_R		0.23
gMVP		0.42
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr12-62894608;