Genetic Variant MON1B:p.Arg154Ser (chr16-77193762-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_014940.4(MON1B):c.460C>A(p.Arg154Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R154C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MON1B
NM_014940.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.09

Publications

0 publications found

Variant links:

Genes affected

MON1B (HGNC:25020): (MON1 homolog B, secretory trafficking associated) Involved in early viral transcription and late viral transcription. Located in cytoplasm. Part of Mon1-Ccz1 complex. [provided by Alliance of Genome Resources, Apr 2022]

MON1B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.919

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014940.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MON1B	NM_014940.4	MANE Select	c.460C>A	p.Arg154Ser	missense	Exon 3 of 6	NP_055755.1	Q7L1V2-1
MON1B	NM_001286639.2		c.149-573C>A		intron	N/A	NP_001273568.1	E7EW32
MON1B	NM_001286640.2		c.38-573C>A		intron	N/A	NP_001273569.1	Q7L1V2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MON1B	ENST00000248248.8	TSL:1 MANE Select	c.460C>A	p.Arg154Ser	missense	Exon 3 of 6	ENSP00000248248.3	Q7L1V2-1
MON1B	ENST00000567291.5	TSL:3	c.460C>A	p.Arg154Ser	missense	Exon 3 of 4	ENSP00000457858.1	H3BUX9
MON1B	ENST00000569610.5	TSL:4	c.460C>A	p.Arg154Ser	missense	Exon 3 of 4	ENSP00000456038.1	H3BR21

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

247924

AF XY:

0.00

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:

6.85e-7

AC:

AN:

1459626

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725912

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33454

American (AMR)

AF:

0.00

AC:

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25932

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110604

Other (OTH)

AF:

0.0000166

AC:

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Uncertain

0.48

BayesDel_addAF

Pathogenic

0.42

BayesDel_noAF

Pathogenic

0.36

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.79

M_CAP

Benign

0.064

MetaRNN

Pathogenic

0.92

MetaSVM

Uncertain

-0.098

MutationAssessor

Uncertain

2.3

PhyloP100

6.1

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.51

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.96

MutPred

0.78

Loss of helix (P = 0.0626)

MVP

0.44

MPC

1.2

ClinPred

0.99

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.64

gMVP

0.82

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