16-77191601-C-G

Position:

• chr16-77191601-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014940.4(MON1B):​c.116C>G​(p.Pro39Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,458,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 0.0000041 (0 hom.)
• Consequence: MON1B NM_014940.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.502

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 (HGNC:):

ACMG classification

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=0.04949832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MON1B	NM_014940.4	c.116C>G	p.Pro39Arg	missense_variant	2/6	ENST00000248248.8	NP_055755.1
MON1B	NM_001286639.2	c.116C>G	p.Pro39Arg	missense_variant	2/5		NP_001273568.1
MON1B	NM_001286640.2	c.37+343C>G		intron_variant			NP_001273569.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MON1B	ENST00000248248.8	c.116C>G	p.Pro39Arg	missense_variant	2/6	1	NM_014940.4	ENSP00000248248.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1458756 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 725840

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2023

The c.116C>G (p.P39R) alteration is located in exon 2 (coding exon 1) of the MON1B gene. This alteration results from a C to G substitution at nucleotide position 116, causing the proline (P) at amino acid position 39 to be replaced by an arginine (R). 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	0.068
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.6
DANN	Benign	0.93
DEOGEN2	Benign	0.027	.;T;T;T;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.69	T;T;T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.049	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	.;L;.;.;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.10	N;N;N;D;D;N
REVEL	Benign	0.011
Sift	Benign	0.10	T;T;T;T;T;D
Sift4G	Benign	0.58	T;T;T;T;.;D
Polyphen		0.0	.;B;.;.;.;B
Vest4		0.28, 0.30
MVP		0.20
MPC		0.39
ClinPred		0.067	T
GERP RS		-2.0
Varity_R		0.033
gMVP		0.15

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

Other links and lift over

dbSNP: rs138570729; hg19: chr16-77225498;