NM_014940.4:c.35C>T

Variant names:

• chr16-77191520-C-T
• rs368005900
• NM_014940.4:c.35C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014940.4(MON1B):​c.35C>T​(p.Pro12Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P12R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MON1B NM_014940.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.29
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26863563).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MON1B	NM_014940.4	MANE Select	c.35C>T	p.Pro12Leu	missense	Exon 2 of 6	NP_055755.1	Q7L1V2-1
	MON1B	NM_001286639.2		c.35C>T	p.Pro12Leu	missense	Exon 2 of 5	NP_001273568.1	E7EW32
	MON1B	NM_001286640.2		c.37+262C>T		intron	N/A	NP_001273569.1	Q7L1V2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MON1B	ENST00000248248.8	TSL:1 MANE Select	c.35C>T	p.Pro12Leu	missense	Exon 2 of 6	ENSP00000248248.3	Q7L1V2-1
	MON1B	ENST00000439557.6	TSL:2	c.35C>T	p.Pro12Leu	missense	Exon 2 of 5	ENSP00000404053.2	E7EW32
	MON1B	ENST00000567291.5	TSL:3	c.35C>T	p.Pro12Leu	missense	Exon 2 of 4	ENSP00000457858.1	H3BUX9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	0.81	L
PhyloP100		3.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.14
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.51
MutPred		0.19		Loss of relative solvent accessibility (P = 0.008)
MVP		0.48
MPC		0.37
ClinPred		0.91	D
GERP RS		4.4
PromoterAI		-0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.13
gMVP		0.31

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

Other links and lift over

dbSNP: rs368005900; hg19: chr16-77225417;