12-123156306-C-G

Position:

• chr12-123156306-C-G

Variant summary

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

The NM_022782.4(MPHOSPH9):​c.*501G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,316 control chromosomes in the GnomAD database, including 53,283 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 0.83 (53252 hom., cov: 33)
  • Exomes 𝑓: 0.79 (31 hom.)
• Consequence: MPHOSPH9 NM_022782.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173

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]

MPHOSPH9 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPHOSPH9	NM_022782.4	c.*501G>C		3_prime_UTR_variant	24/24	ENST00000606320.6	NP_073619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPHOSPH9	ENST00000606320	c.*501G>C		3_prime_UTR_variant	24/24	5	NM_022782.4	ENSP00000475489.1
MPHOSPH9	ENST00000541603.6	c.553-3681G>C		intron_variant		1		ENSP00000446362.2
MPHOSPH9	ENST00000541076	c.*501G>C		3_prime_UTR_variant	22/22	5		ENSP00000445859.2

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126840 AN: 152098 Hom.: 53197 Cov.: 33

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.828

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.824

GnomAD4 exome AF: 0.794 AC: 81 AN: 102 Hom.: 31 Cov.: 0 AF XY: 0.729 AC XY: 35 AN XY: 48

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 0.806

Gnomad4 NFE exome AF: 0.780

Gnomad4 OTH exome AF: 0.700

GnomAD4 genome AF: 0.834 AC: 126947 AN: 152214 Hom.: 53252 Cov.: 33 AF XY: 0.833 AC XY: 61981 AN XY: 74410

Gnomad4 AFR AF: 0.910

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.803

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.827

Alfa AF: 0.819 Hom.: 6363

Bravo AF: 0.839

Asia WGS AF: 0.871 AC: 3025 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.48

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: rs1727313; hg19: chr12-123640853;