Genetic Variant MON1B:p.Ser133Thr (chr16-77193699-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_014940.4(MON1B):c.397T>A(p.Ser133Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,738 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MON1B
NM_014940.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.41

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.397T>A	p.Ser133Thr	missense	Exon 3 of 6	NP_055755.1	Q7L1V2-1
MON1B	NM_001286639.2		c.149-636T>A		intron	N/A	NP_001273568.1	E7EW32
MON1B	NM_001286640.2		c.38-636T>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.397T>A	p.Ser133Thr	missense	Exon 3 of 6	ENSP00000248248.3	Q7L1V2-1
MON1B	ENST00000567291.5	TSL:3	c.397T>A	p.Ser133Thr	missense	Exon 3 of 4	ENSP00000457858.1	H3BUX9
MON1B	ENST00000569610.5	TSL:4	c.397T>A	p.Ser133Thr	missense	Exon 3 of 4	ENSP00000456038.1	H3BR21

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

250304

AF XY:

0.0000148

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:

0.000164

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461738

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111936

Other (OTH)

AF:

0.0000166

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

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.:

Alfa

AF:

0.000111

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.62

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.8

PhyloP100

3.4

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.99

REVEL

Benign

0.23

Sift

Benign

0.034

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.77

MutPred

0.67

Loss of phosphorylation at S128 (P = 0.1242)

MVP

0.41

MPC

1.0

ClinPred

0.57

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.15

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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