rs780288947

Variant names:

• chr16-77194622-C-A
• rs780288947
• NM_014940.4:c.763C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-77194622-C-A
• chr16-77194622-C-G
• chr16-77194622-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014940.4(MON1B):​c.763C>A​(p.Arg255Ser) 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. 15/21 in silico tools predict 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. R255H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MON1B NM_014940.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05958426).

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.763C>A	p.Arg255Ser	missense	Exon 4 of 6	NP_055755.1	Q7L1V2-1
	MON1B	NM_001286639.2		c.436C>A	p.Arg146Ser	missense	Exon 3 of 5	NP_001273568.1	E7EW32
	MON1B	NM_001286640.2		c.325C>A	p.Arg109Ser	missense	Exon 2 of 4	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.763C>A	p.Arg255Ser	missense	Exon 4 of 6	ENSP00000248248.3	Q7L1V2-1
	MON1B	ENST00000439557.6	TSL:2	c.436C>A	p.Arg146Ser	missense	Exon 3 of 5	ENSP00000404053.2	E7EW32
	MON1B	ENST00000545553.1	TSL:2	c.325C>A	p.Arg109Ser	missense	Exon 2 of 4	ENSP00000444881.1	Q7L1V2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Benign	0.84
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.6	N
PhyloP100		0.38
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	2.4	N
REVEL	Benign	0.085
Sift	Benign	0.81	T
Sift4G	Benign	1.0	T
Polyphen		0.027	B
Vest4		0.091
MutPred		0.35		Loss of MoRF binding (P = 0.0615)
MVP		0.18
MPC		0.45
ClinPred		0.65	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.096
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs780288947; hg19: chr16-77228519;