Variant 16-77193495-C-A 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.193C>A(p.Gln65Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000829 in 1,447,218 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

MON1B
NM_014940.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07

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 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=0.04157579).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MON1B	NM_014940.4 linkuse as main transcript	c.193C>A	p.Gln65Lys	missense_variant	3/6	ENST00000248248.8	NP_055755.1	Q7L1V2-1Q6ZR87
MON1B	NM_001286639.2 linkuse as main transcript	c.149-840C>A		intron_variant			NP_001273568.1	Q7L1V2E7EW32Q6ZR87B4DKA0
MON1B	NM_001286640.2 linkuse as main transcript	c.38-840C>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.193C>A	p.Gln65Lys	missense_variant	3/6	1	NM_014940.4	ENSP00000248248.3		Q7L1V2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000249

AC:

AN:

240968

Hom.:

AF XY:

0.0000308

AC XY:

AN XY:

129746

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 SAS exome

AF:

0.000210

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000829

AC:

AN:

1447218

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

718214

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:

0.000142

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000412

AC:

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 27, 2024

The c.193C>A (p.Q65K) alteration is located in exon 3 (coding exon 2) of the MON1B gene. This alteration results from a C to A substitution at nucleotide position 193, causing the glutamine (Q) at amino acid position 65 to be replaced by a lysine (K). 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

0.087

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.41

CADD

Benign

8.3

DANN

Benign

0.92

DEOGEN2

Benign

0.029

.;T;T;T;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.63

T;T;T;T;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.042

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

.;L;.;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.10

N;N;N;D;D

REVEL

Benign

0.075

Sift

Uncertain

0.012

D;D;D;T;T

Sift4G

Benign

0.63

T;T;T;D;.

Polyphen

0.0030

.;B;.;.;.

Vest4

0.29

MutPred

0.19

Gain of ubiquitination at Q65 (P = 0.0045);Gain of ubiquitination at Q65 (P = 0.0045);Gain of ubiquitination at Q65 (P = 0.0045);Gain of ubiquitination at Q65 (P = 0.0045);Gain of ubiquitination at Q65 (P = 0.0045);

MVP

0.23

MPC

0.47

ClinPred

0.033

GERP RS

2.4

Varity_R

0.072

gMVP

0.35

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