2-71130375-C-G

Variant names:

• chr2-71130375-C-G
• rs11126320
• ENST00000498451.3:c.-291C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000498451.3(MPHOSPH10):​c.-291C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 698,798 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.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MPHOSPH10 ENST00000498451.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621
• 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]

MCEE (HGNC:16732): (methylmalonyl-CoA epimerase) The product of this gene catalyzes the interconversion of D- and L-methylmalonyl-CoA during the degradation of branched chain amino acids. odd chain-length fatty acids, and other metabolites. Mutations in this gene result in methylmalonyl-CoA epimerase deficiency, which is presented as mild to moderate methylmalonic aciduria. [provided by RefSeq, Jul 2008]

MCEE Gene-Disease associations (from GenCC):

• methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000498451.3. 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
	MCEE	NM_032601.4	MANE Select	c.-156G>C		upstream_gene	N/A	NP_115990.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPHOSPH10	ENST00000498451.3	TSL:1	c.-291C>G		5_prime_UTR	Exon 1 of 5	ENSP00000475545.1	U3KQ48
	MPHOSPH10	ENST00000468427.2	TSL:4	c.-802C>G		5_prime_UTR	Exon 1 of 11	ENSP00000511582.1	A0A8Q3WK70
	MPHOSPH10	ENST00000695484.2		n.-291C>G		non_coding_transcript_exon	Exon 1 of 11	ENSP00000511956.1	A0A8Q3WKH7

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000143 AC: 1 AN: 698798 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 367976

African (AFR) AF: 0.0000553 AC: 1 AN: 18084

American (AMR) AF: 0.00 AC: 0 AN: 34686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20550

East Asian (EAS) AF: 0.00 AC: 0 AN: 32556

South Asian (SAS) AF: 0.00 AC: 0 AN: 64644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3426

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 442520

Other (OTH) AF: 0.00 AC: 0 AN: 34952

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.1
DANN	Benign	0.46
PhyloP100		-0.62
PromoterAI		-0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs11126320; hg19: chr2-71357505;