rs1716167

chr12-123166615-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPHOSPH9	NM_022782.4	c.2591+40T>C		intron_variant		ENST00000606320.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPHOSPH9	ENST00000606320.6	c.2591+40T>C		intron_variant		5	NM_022782.4	P1

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

GnomAD3 exomes AF: 0.742 AC: 174302 AN: 234988 Hom.: 67596 AF XY: 0.750 AC XY: 95375 AN XY: 127250

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 SAS exome AF: 0.727

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

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.726

Gnomad4 ASJ exome AF: 0.689

Gnomad4 EAS exome AF: 0.975

Gnomad4 SAS exome AF: 0.725

Gnomad4 FIN exome AF: 0.808

Gnomad4 NFE exome AF: 0.784

Gnomad4 OTH exome AF: 0.751

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

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.675

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.023
Dann	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1716167; hg19: chr12-123651162;