12-123166615-A-G

Variant names:

• chr12-123166615-A-G
• rs1716167
• NM_022782.4:c.2591+40T>C

Variant summary

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

The NM_022782.4(MPHOSPH9):​c.2591+40T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 1,594,036 control chromosomes in the GnomAD database, including 468,615 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 0.63 (35246 hom., cov: 33)
  • Exomes 𝑓: 0.77 (433369 hom.)
• Consequence: MPHOSPH9 NM_022782.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809
• Publications: 28 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPHOSPH9	NM_022782.4	MANE Select	c.2591+40T>C		intron	N/A	NP_073619.3
	MPHOSPH9	NR_103517.2		n.2555+40T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPHOSPH9	ENST00000606320.6	TSL:5 MANE Select	c.2591+40T>C		intron	N/A	ENSP00000475489.1
	MPHOSPH9	ENST00000302373.8	TSL:1	n.2069+40T>C		intron	N/A	ENSP00000304096.5
	MPHOSPH9	ENST00000539024.5	TSL:1	n.1571+40T>C		intron	N/A	ENSP00000441764.1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96558 AN: 152056 Hom.: 35239 Cov.: 33

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.672

GnomAD2 exomes AF: 0.742 AC: 174302 AN: 234988 AF XY: 0.750

Gnomad AFR exome AF: 0.232

Gnomad AMR exome AF: 0.726

Gnomad ASJ exome AF: 0.690

Gnomad EAS exome AF: 0.975

Gnomad FIN exome AF: 0.807

Gnomad NFE exome AF: 0.777

Gnomad OTH exome AF: 0.760

GnomAD4 exome AF: 0.769 AC: 1109312 AN: 1441862 Hom.: 433369 Cov.: 32 AF XY: 0.768 AC XY: 551088 AN XY: 717272

African (AFR) AF: 0.227 AC: 7346 AN: 32376

American (AMR) AF: 0.726 AC: 28352 AN: 39062

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 17567 AN: 25492

East Asian (EAS) AF: 0.975 AC: 38279 AN: 39270

South Asian (SAS) AF: 0.725 AC: 59595 AN: 82192

European-Finnish (FIN) AF: 0.808 AC: 43017 AN: 53268

Middle Eastern (MID) AF: 0.652 AC: 3676 AN: 5642

European-Non Finnish (NFE) AF: 0.784 AC: 866670 AN: 1104912

Other (OTH) AF: 0.751 AC: 44810 AN: 59648

GnomAD4 genome AF: 0.635 AC: 96591 AN: 152174 Hom.: 35246 Cov.: 33 AF XY: 0.641 AC XY: 47709 AN XY: 74390

African (AFR) AF: 0.250 AC: 10387 AN: 41516

American (AMR) AF: 0.735 AC: 11235 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2319 AN: 3468

East Asian (EAS) AF: 0.972 AC: 5038 AN: 5184

South Asian (SAS) AF: 0.731 AC: 3533 AN: 4832

European-Finnish (FIN) AF: 0.802 AC: 8485 AN: 10584

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.783 AC: 53234 AN: 67998

Other (OTH) AF: 0.675 AC: 1428 AN: 2114

Alfa AF: 0.685 Hom.: 13244

Bravo AF: 0.611

Asia WGS AF: 0.820 AC: 2850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.023
DANN	Benign	0.60
PhyloP100		-0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1716167; hg19: chr12-123651162;