ENST00000545406.1:c.-158-2872A>C

Variant names:

• chr12-123233394-T-G
• rs1314198112
• ENST00000545406.1:c.-158-2872A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000545406.1(MPHOSPH9):​c.-158-2872A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: MPHOSPH9 ENST00000545406.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166

Genes affected

MPHOSPH9 (HGNC:7215): (M-phase phosphoprotein 9) Located in Golgi apparatus and centriole. Implicated in multiple sclerosis. [provided by Alliance of Genome Resources, Apr 2022]

MTRFR (HGNC:26784): (mitochondrial translation release factor in rescue) This nuclear gene encodes a mitochondrial matrix protein that appears to contribute to peptide chain termination in the mitochondrial translation machinery. Two different 1 bp deletions (resulting in the same premature stop codon)result in decreased mitochondrial translation, decreased levels of oxidative phosphorylation complexes and encepthalomyopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPHOSPH9	XM_017018673.2	c.-158-2872A>C		intron_variant	Intron 1 of 24		XP_016874162.1
MTRFR	XM_047429877.1	c.-29+12T>G		intron_variant	Intron 1 of 2		XP_047285833.1
MTRFR	NM_152269.5	c.-166T>G		upstream_gene_variant		ENST00000253233.6	NP_689482.1
MTRFR	NM_001194995.1	c.-559T>G		upstream_gene_variant			NP_001181924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTRFR	ENST00000253233.6	c.-166T>G		upstream_gene_variant		1	NM_152269.5	ENSP00000253233.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.1
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs1314198112; hg19: chr12-123717941;