rs1790100

Positions:

• chr12-123172178-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022782.4(MPHOSPH9):​c.2456+4510C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 152,096 control chromosomes in the GnomAD database, including 35,858 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 0.64 (35858 hom., cov: 32)
• Consequence: MPHOSPH9 NM_022782.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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=-1.06).
• 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	Protein	UniProt
MPHOSPH9	NM_022782.4	c.2456+4510C>A		intron_variant		ENST00000606320.6	NP_073619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPHOSPH9	ENST00000606320.6	c.2456+4510C>A		intron_variant		5	NM_022782.4	ENSP00000475489	P1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97668 AN: 151978 Hom.: 35853 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.828

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.642 AC: 97693 AN: 152096 Hom.: 35858 Cov.: 32 AF XY: 0.649 AC XY: 48284 AN XY: 74354

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.738

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.774

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.681

Alfa AF: 0.735 Hom.: 11935

Bravo AF: 0.619

Asia WGS AF: 0.849 AC: 2949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.23
DANN	Benign	0.51

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: rs1790100; hg19: chr12-123656725;