rs184689442

Variant names:

• chr2-71130360-C-T
• rs184689442
• ENST00000498451.3:c.-306C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-71130360-C-T
• chr2-71130360-C-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000498451.3(MPHOSPH10):​c.-306C>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 0.00708 in 892,788 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (10 hom., cov: 34)
  • Exomes 𝑓: 0.0073 (25 hom.)
• Consequence: MPHOSPH10 ENST00000498451.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.695
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-71130360-C-T is Benign according to our data. Variant chr2-71130360-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1325930.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

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.-141G>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.-306C>T		5_prime_UTR	Exon 1 of 5	ENSP00000475545.1	U3KQ48
	MPHOSPH10	ENST00000468427.2	TSL:4	c.-817C>T		5_prime_UTR	Exon 1 of 11	ENSP00000511582.1	A0A8Q3WK70
	MPHOSPH10	ENST00000695484.2		n.-306C>T		non_coding_transcript_exon	Exon 1 of 11	ENSP00000511956.1	A0A8Q3WKH7

Frequencies

GnomAD3 genomes AF: 0.00621 AC: 946 AN: 152218 Hom.: 10 Cov.: 34

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0232

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00839

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.00725 AC: 5371 AN: 740452 Hom.: 25 Cov.: 10 AF XY: 0.00703 AC XY: 2729 AN XY: 388164

African (AFR) AF: 0.00121 AC: 23 AN: 18978

American (AMR) AF: 0.00255 AC: 89 AN: 34860

Ashkenazi Jewish (ASJ) AF: 0.00306 AC: 64 AN: 20938

East Asian (EAS) AF: 0.00 AC: 0 AN: 32808

South Asian (SAS) AF: 0.00120 AC: 79 AN: 65812

European-Finnish (FIN) AF: 0.0260 AC: 1234 AN: 47484

Middle Eastern (MID) AF: 0.000798 AC: 3 AN: 3760

European-Non Finnish (NFE) AF: 0.00763 AC: 3661 AN: 479540

Other (OTH) AF: 0.00601 AC: 218 AN: 36272

GnomAD4 genome AF: 0.00622 AC: 948 AN: 152336 Hom.: 10 Cov.: 34 AF XY: 0.00673 AC XY: 501 AN XY: 74484

African (AFR) AF: 0.00111 AC: 46 AN: 41580

American (AMR) AF: 0.00385 AC: 59 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4826

European-Finnish (FIN) AF: 0.0232 AC: 246 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00842 AC: 573 AN: 68026

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.00767 Hom.: 1

Bravo AF: 0.00416

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.8
DANN	Benign	0.80
PhyloP100		-0.69
PromoterAI		-0.21	Neutral
Mutation Taster		=300/0	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: rs184689442; hg19: chr2-71357490;