2-71130504-C-T

Variant names:

• chr2-71130504-C-T
• rs1813348
• ENST00000498451.3:c.-162C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000498451.3(MPHOSPH10):​c.-162C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 830,438 control chromosomes in the GnomAD database, including 166,660 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (25028 hom., cov: 35)
  • Exomes 𝑓: 0.64 (141632 hom.)
• Consequence: MPHOSPH10 ENST00000498451.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0670
• Publications: 6 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-71130504-C-T is Benign according to our data. Variant chr2-71130504-C-T is described in ClinVar as Benign. ClinVar VariationId is 1222521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

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
	MPHOSPH10	NM_005791.3	MANE Select	c.-162C>T		upstream_gene	N/A	NP_005782.1	O00566

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPHOSPH10	ENST00000498451.3	TSL:1	c.-162C>T		5_prime_UTR	Exon 1 of 5	ENSP00000475545.1	U3KQ48
	MPHOSPH10	ENST00000468427.2	TSL:4	c.-673C>T		5_prime_UTR	Exon 1 of 11	ENSP00000511582.1	A0A8Q3WK70
	MPHOSPH10	ENST00000695484.2		n.-162C>T		non_coding_transcript_exon	Exon 1 of 11	ENSP00000511956.1	A0A8Q3WKH7

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82735 AN: 152096 Hom.: 25032 Cov.: 35

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.567

GnomAD4 exome AF: 0.638 AC: 432894 AN: 678222 Hom.: 141632 Cov.: 9 AF XY: 0.641 AC XY: 221679 AN XY: 345738

African (AFR) AF: 0.254 AC: 4325 AN: 17032

American (AMR) AF: 0.667 AC: 13739 AN: 20606

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 11135 AN: 15370

East Asian (EAS) AF: 0.363 AC: 11671 AN: 32120

South Asian (SAS) AF: 0.634 AC: 32252 AN: 50898

European-Finnish (FIN) AF: 0.656 AC: 22649 AN: 34540

Middle Eastern (MID) AF: 0.633 AC: 1540 AN: 2432

European-Non Finnish (NFE) AF: 0.667 AC: 314785 AN: 471740

Other (OTH) AF: 0.621 AC: 20798 AN: 33484

GnomAD4 genome AF: 0.544 AC: 82755 AN: 152216 Hom.: 25028 Cov.: 35 AF XY: 0.547 AC XY: 40731 AN XY: 74428

African (AFR) AF: 0.268 AC: 11116 AN: 41536

American (AMR) AF: 0.643 AC: 9832 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2499 AN: 3472

East Asian (EAS) AF: 0.332 AC: 1723 AN: 5182

South Asian (SAS) AF: 0.618 AC: 2984 AN: 4826

European-Finnish (FIN) AF: 0.670 AC: 7097 AN: 10596

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.670 AC: 45539 AN: 67990

Other (OTH) AF: 0.563 AC: 1191 AN: 2114

Alfa AF: 0.535 Hom.: 5610

Bravo AF: 0.529

Asia WGS AF: 0.431 AC: 1499 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.93
PhyloP100		0.067
PromoterAI		0.029	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs1813348; hg19: chr2-71357634; COSMIC: COSV54907692; COSMIC: COSV54907692;