rs11126320

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-71130375-C-T
• chr2-71130375-C-A
• chr2-71130375-C-G

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.-291C>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 0.0138 in 851,090 control chromosomes in the GnomAD database, including 589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (374 hom., cov: 34)
  • Exomes 𝑓: 0.0080 (215 hom.)
• Consequence: MPHOSPH10 ENST00000498451.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.621
• Publications: 4 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=-0.85).
• BP6: Variant 2-71130375-C-T is Benign according to our data. Variant chr2-71130375-C-T is described in ClinVar as Benign. ClinVar VariationId is 1237378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 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
	MCEE	NM_032601.4	MANE Select	c.-156G>A		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>T		5_prime_UTR	Exon 1 of 5	ENSP00000475545.1	U3KQ48
	MPHOSPH10	ENST00000468427.2	TSL:4	c.-802C>T		5_prime_UTR	Exon 1 of 11	ENSP00000511582.1	A0A8Q3WK70
	MPHOSPH10	ENST00000695484.2		n.-291C>T		non_coding_transcript_exon	Exon 1 of 11	ENSP00000511956.1	A0A8Q3WKH7

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6192 AN: 152192 Hom.: 372 Cov.: 34

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0172

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00961

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00304

Gnomad OTH AF: 0.0282

GnomAD4 exome AF: 0.00800 AC: 5589 AN: 698780 Hom.: 215 Cov.: 9 AF XY: 0.00744 AC XY: 2737 AN XY: 367962

African (AFR) AF: 0.135 AC: 2439 AN: 18078

American (AMR) AF: 0.00899 AC: 312 AN: 34686

Ashkenazi Jewish (ASJ) AF: 0.00122 AC: 25 AN: 20550

East Asian (EAS) AF: 0.00544 AC: 177 AN: 32554

South Asian (SAS) AF: 0.0127 AC: 820 AN: 64642

European-Finnish (FIN) AF: 0.000106 AC: 5 AN: 47380

Middle Eastern (MID) AF: 0.0131 AC: 45 AN: 3426

European-Non Finnish (NFE) AF: 0.00269 AC: 1192 AN: 442512

Other (OTH) AF: 0.0164 AC: 574 AN: 34952

GnomAD4 genome AF: 0.0407 AC: 6193 AN: 152310 Hom.: 374 Cov.: 34 AF XY: 0.0388 AC XY: 2891 AN XY: 74490

African (AFR) AF: 0.134 AC: 5546 AN: 41542

American (AMR) AF: 0.0171 AC: 262 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00963 AC: 50 AN: 5190

South Asian (SAS) AF: 0.0126 AC: 61 AN: 4832

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00304 AC: 207 AN: 68032

Other (OTH) AF: 0.0279 AC: 59 AN: 2114

Alfa AF: 0.0257 Hom.: 72

Bravo AF: 0.0469

Asia WGS AF: 0.0150 AC: 53 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	-0.85
CADD	Benign	4.7
DANN	Benign	0.78
PhyloP100		-0.62
PromoterAI		-0.076	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs11126320; hg19: chr2-71357505;