12-123166736-T-C

Position:

• chr12-123166736-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022782.4(MPHOSPH9):​c.2510A>G​(p.Glu837Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MPHOSPH9 NM_022782.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.32

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31103235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPHOSPH9	NM_022782.4	c.2510A>G	p.Glu837Gly	missense_variant	17/24	ENST00000606320.6	NP_073619.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPHOSPH9	ENST00000606320.6	c.2510A>G	p.Glu837Gly	missense_variant	17/24	5	NM_022782.4	ENSP00000475489	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461762 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727178

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2024

The c.2054A>G (p.E685G) alteration is located in exon 13 (coding exon 13) of the MPHOSPH9 gene. This alteration results from a A to G substitution at nucleotide position 2054, causing the glutamic acid (E) at amino acid position 685 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.14	T;T;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.7	.;M;.
MutationTaster	Benign	0.87	D;D
PrimateAI	Benign	0.45	T
REVEL	Benign	0.23
Sift4G	Benign	0.32	T;T;D
Vest4		0.45
MVP		0.35
ClinPred		0.90	D
GERP RS		4.0
Varity_R		0.14
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-123651283;