12-123161256-G-C

Variant names:

• chr12-123161256-G-C
• rs1051431
• NM_022782.4:c.3261C>G

Variant summary

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

The NM_022782.4(MPHOSPH9):​c.3261C>G​(p.Tyr1087*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 31)
• Consequence: MPHOSPH9 NM_022782.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399
• Publications: 43 publications found

Genes affected

MPHOSPH9 (HGNC:7215): (M-phase phosphoprotein 9) Located in Golgi apparatus and centriole. Implicated in multiple sclerosis. [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_022782.4. 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
	MPHOSPH9	NM_022782.4	MANE Select	c.3261C>G	p.Tyr1087*	stop_gained	Exon 22 of 24	NP_073619.3
	MPHOSPH9	NR_103517.2		n.3225C>G		non_coding_transcript_exon	Exon 22 of 24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPHOSPH9	ENST00000606320.6	TSL:5 MANE Select	c.3261C>G	p.Tyr1087*	stop_gained	Exon 22 of 24	ENSP00000475489.1	Q99550-1
	MPHOSPH9	ENST00000541603.6	TSL:1	c.363C>G	p.Tyr121*	stop_gained	Exon 4 of 6	ENSP00000446362.2	F5H1U6
	MPHOSPH9	ENST00000302373.8	TSL:1	n.*112C>G		non_coding_transcript_exon	Exon 16 of 18	ENSP00000304096.5	J3KNE4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 71

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	34
DANN	Uncertain	0.99
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.034	N
PhyloP100		-0.40
Vest4		0.14
GERP RS		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=29/171	disease causing (fs/PTC)

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: rs1051431; hg19: chr12-123645803;