2-71133527-T-A

Variant names:

• chr2-71133527-T-A
• rs147378452
• NM_005791.3:c.719T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005791.3(MPHOSPH10):​c.719T>A​(p.Ile240Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I240T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MPHOSPH10 NM_005791.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.83
• Publications: 0 publications found

Genes affected

MPHOSPH10 (HGNC:7213): (M-phase phosphoprotein 10) This gene encodes a protein that is phosphorylated during mitosis. The protein localizes to the nucleolus during interphase and to the chromosomes during M phase. The protein associates with the U3 small nucleolar ribonucleoprotein 60-80S complexes and may be involved in pre-rRNA processing. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16669494).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005791.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPHOSPH10	NM_005791.3	MANE Select	c.719T>A	p.Ile240Asn	missense	Exon 2 of 11	NP_005782.1	O00566

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPHOSPH10	ENST00000244230.7	TSL:1 MANE Select	c.719T>A	p.Ile240Asn	missense	Exon 2 of 11	ENSP00000244230.2	O00566
	MPHOSPH10	ENST00000498451.3	TSL:1	c.719T>A	p.Ile240Asn	missense	Exon 2 of 5	ENSP00000475545.1	U3KQ48
	MPHOSPH10	ENST00000857231.1		c.719T>A	p.Ile240Asn	missense	Exon 2 of 11	ENSP00000527290.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458584 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 725734

African (AFR) AF: 0.00 AC: 0 AN: 33148

American (AMR) AF: 0.00 AC: 0 AN: 43944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25970

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 85722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110922

Other (OTH) AF: 0.00 AC: 0 AN: 60160

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.8
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.19
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.049	D
Polyphen		0.90	P
Vest4		0.27
MutPred		0.39		Loss of stability (P = 0.0415)
MVP		0.25
MPC		0.51
ClinPred		0.98	D
GERP RS		4.9
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1
Varity_R		0.25
gMVP		0.077
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs147378452; hg19: chr2-71360657;