12-123214056-A-T

Variant names:

• chr12-123214056-A-T
• rs1727324
• NM_022782.4:c.1087+688T>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.1087+688T>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 152,076 control chromosomes in the GnomAD database, including 54,545 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 (54545 hom., cov: 30)
• Consequence: MPHOSPH9 NM_022782.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326
• Publications: 16 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPHOSPH9	NM_022782.4	c.1087+688T>A		intron_variant	Intron 7 of 23	ENST00000606320.6	NP_073619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPHOSPH9	ENST00000606320.6	c.1087+688T>A		intron_variant	Intron 7 of 23	5	NM_022782.4	ENSP00000475489.1

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128244 AN: 151958 Hom.: 54487 Cov.: 30

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.828

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.783

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: 128353 AN: 152076 Hom.: 54545 Cov.: 30 AF XY: 0.843 AC XY: 62664 AN XY: 74324

African (AFR) AF: 0.932 AC: 38702 AN: 41506

American (AMR) AF: 0.825 AC: 12584 AN: 15256

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

East Asian (EAS) AF: 0.996 AC: 5147 AN: 5170

South Asian (SAS) AF: 0.783 AC: 3772 AN: 4818

European-Finnish (FIN) AF: 0.803 AC: 8484 AN: 10564

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

European-Non Finnish (NFE) AF: 0.799 AC: 54338 AN: 67976

Other (OTH) AF: 0.834 AC: 1760 AN: 2110

Alfa AF: 0.823 Hom.: 6061

Bravo AF: 0.850

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.083
DANN	Benign	0.40
PhyloP100		-0.33
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: rs1727324; hg19: chr12-123698603;