12-123204974-C-T

Variant names:

• chr12-123204974-C-T
• rs2695478
• NM_022782.4:c.1195-1599G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022782.4(MPHOSPH9):​c.1195-1599G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 152,204 control chromosomes in the GnomAD database, including 54,589 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (54589 hom., cov: 32)
• Consequence: MPHOSPH9 NM_022782.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59
• Publications: 26 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

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.1195-1599G>A		intron	N/A	NP_073619.3
	MPHOSPH9	NR_103517.2		n.1484-1599G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPHOSPH9	ENST00000606320.6	TSL:5 MANE Select	c.1195-1599G>A		intron	N/A	ENSP00000475489.1
	MPHOSPH9	ENST00000302373.8	TSL:1	n.799-1890G>A		intron	N/A	ENSP00000304096.5
	MPHOSPH9	ENST00000539024.5	TSL:1	n.301-1890G>A		intron	N/A	ENSP00000441764.1

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128343 AN: 152086 Hom.: 54532 Cov.: 32

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.832

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.844 AC: 128451 AN: 152204 Hom.: 54589 Cov.: 32 AF XY: 0.843 AC XY: 62732 AN XY: 74418

African (AFR) AF: 0.932 AC: 38750 AN: 41556

American (AMR) AF: 0.824 AC: 12592 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2598 AN: 3470

East Asian (EAS) AF: 0.996 AC: 5155 AN: 5178

South Asian (SAS) AF: 0.783 AC: 3773 AN: 4816

European-Finnish (FIN) AF: 0.803 AC: 8504 AN: 10594

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.799 AC: 54346 AN: 67996

Other (OTH) AF: 0.834 AC: 1765 AN: 2116

Alfa AF: 0.812 Hom.: 64503

Bravo AF: 0.850

Asia WGS AF: 0.900 AC: 3127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.047
DANN	Benign	0.84
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs2695478; hg19: chr12-123689521;