12-123204974-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPHOSPH9	NM_022782.4	c.1195-1599G>A		intron_variant		ENST00000606320.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPHOSPH9	ENST00000606320.6	c.1195-1599G>A		intron_variant		5	NM_022782.4	P1

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

Gnomad4 AFR AF: 0.932

Gnomad4 AMR AF: 0.824

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.783

Gnomad4 FIN AF: 0.803

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.834

Alfa AF: 0.806 Hom.: 48665

Bravo AF: 0.850

Asia WGS AF: 0.900 AC: 3127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.047
Dann	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs2695478; hg19: chr12-123689521;