Variant 16-77193480-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014940.4(MON1B):c.178C>G(p.Pro60Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,579,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

MON1B
NM_014940.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39

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:

MON1B (HGNC:):

MON1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012742668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MON1B	NM_014940.4 linkuse as main transcript	c.178C>G	p.Pro60Ala	missense_variant	3/6	ENST00000248248.8	NP_055755.1	Q7L1V2-1Q6ZR87
MON1B	NM_001286639.2 linkuse as main transcript	c.149-855C>G		intron_variant			NP_001273568.1	Q7L1V2E7EW32Q6ZR87B4DKA0
MON1B	NM_001286640.2 linkuse as main transcript	c.38-855C>G		intron_variant			NP_001273569.1	Q7L1V2-2Q6ZR87

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MON1B	ENST00000248248.8 linkuse as main transcript	c.178C>G	p.Pro60Ala	missense_variant	3/6	1	NM_014940.4	ENSP00000248248.3		Q7L1V2-1

Frequencies

GnomAD3 genomes

AF:

0.000552

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000159

AC:

AN:

226124

Hom.:

AF XY:

0.000116

AC XY:

AN XY:

121114

show subpopulations

Gnomad AFR exome

AF:

0.00181

Gnomad AMR exome

AF:

0.000127

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0000392

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000743

AC:

106

AN:

1427240

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

705934

show subpopulations

Gnomad4 AFR exome

AF:

0.00282

Gnomad4 AMR exome

AF:

0.0000726

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000246

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000136

GnomAD4 genome

AF:

0.000552

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000544

Hom.:

Bravo

AF:

0.000710

ESP6500AA

AF:

0.00205

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 09, 2021

The c.178C>G (p.P60A) alteration is located in exon 3 (coding exon 2) of the MON1B gene. This alteration results from a C to G substitution at nucleotide position 178, causing the proline (P) at amino acid position 60 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

8.9

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

.;T;T;T;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.45

T;T;T;T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.013

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;.;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

0.82

N;N;N;D;D

REVEL

Benign

0.083

Sift

Benign

0.76

T;T;T;T;T

Sift4G

Benign

0.80

T;T;T;T;.

Polyphen

0.0010

.;B;.;.;.

Vest4

0.18

MVP

0.13

MPC

0.37

ClinPred

0.0076

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.022

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over