16-77193495-C-T

Variant names:

• chr16-77193495-C-T
• rs753553964
• NM_014940.4:c.193C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014940.4(MON1B):​c.193C>T​(p.Gln65*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MON1B NM_014940.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.193C>T	p.Gln65*	stop_gained	Exon 3 of 6	NP_055755.1	Q7L1V2-1
	MON1B	NM_001286639.2		c.149-840C>T		intron	N/A	NP_001273568.1	E7EW32
	MON1B	NM_001286640.2		c.38-840C>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.193C>T	p.Gln65*	stop_gained	Exon 3 of 6	ENSP00000248248.3	Q7L1V2-1
	MON1B	ENST00000567291.5	TSL:3	c.193C>T	p.Gln65*	stop_gained	Exon 3 of 4	ENSP00000457858.1	H3BUX9
	MON1B	ENST00000569610.5	TSL:4	c.193C>T	p.Gln65*	stop_gained	Exon 3 of 4	ENSP00000456038.1	H3BR21

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447218 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 718214

African (AFR) AF: 0.00 AC: 0 AN: 33278

American (AMR) AF: 0.00 AC: 0 AN: 43796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24956

East Asian (EAS) AF: 0.00 AC: 0 AN: 39534

South Asian (SAS) AF: 0.00 AC: 0 AN: 84254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1103138

Other (OTH) AF: 0.00 AC: 0 AN: 59698

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	35
DANN	Uncertain	1.0
Eigen	Benign	0.17
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.31	N
PhyloP100		1.1
Vest4		0.23
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs753553964; hg19: chr16-77227392;