Variant 16-77191537-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014940.4(MON1B):c.52T>A(p.Leu18Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,457,698 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: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

MON1B
NM_014940.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0590

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.106746376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MON1B	NM_014940.4 linkuse as main transcript	c.52T>A	p.Leu18Met	missense_variant	2/6	ENST00000248248.8	NP_055755.1	Q7L1V2-1Q6ZR87
MON1B	NM_001286639.2 linkuse as main transcript	c.52T>A	p.Leu18Met	missense_variant	2/5		NP_001273568.1	Q7L1V2E7EW32Q6ZR87B4DKA0
MON1B	NM_001286640.2 linkuse as main transcript	c.37+279T>A		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.52T>A	p.Leu18Met	missense_variant	2/6	1	NM_014940.4	ENSP00000248248.3		Q7L1V2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1457698

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725306

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.00144

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

Jul 14, 2023

The c.52T>A (p.L18M) alteration is located in exon 2 (coding exon 1) of the MON1B gene. This alteration results from a T to A substitution at nucleotide position 52, causing the leucine (L) at amino acid position 18 to be replaced by a methionine (M). 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

0.088

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.030

.;T;T;T;T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.70

T;T;T;T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.11

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

.;L;.;.;.;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.040

N;N;N;N;N;N

REVEL

Benign

0.061

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Benign

0.29

T;T;T;.;.;T

Polyphen

0.84, 0.92

.;P;.;.;.;P

Vest4

0.45, 0.46

MutPred

0.28

Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);

MVP

0.34

MPC

0.70

ClinPred

0.46

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.084

gMVP

0.10

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

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