chr17-18263170-C-T

Position:

• chr17-18263170-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139162.4(MIEF2):​c.232C>T​(p.Pro78Ser) variant causes a missense 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MIEF2 NM_139162.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.784

Genes affected

MIEF2 (HGNC:17920): (mitochondrial elongation factor 2) This gene encodes an outer mitochondrial membrane protein that functions in the regulation of mitochondrial morphology. It can directly recruit the fission mediator dynamin-related protein 1 (Drp1) to the mitochondrial surface. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2011]

MIEF2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07103181).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIEF2	NM_139162.4	c.232C>T	p.Pro78Ser	missense_variant	3/4	ENST00000323019.9	NP_631901.2
MIEF2	NM_148886.2	c.265C>T	p.Pro89Ser	missense_variant	3/4		NP_683684.2
MIEF2	NM_001144900.3	c.232C>T	p.Pro78Ser	missense_variant	3/4		NP_001138372.1
MIEF2	XM_017024190.2	c.253C>T	p.Pro85Ser	missense_variant	3/4		XP_016879679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIEF2	ENST00000323019.9	c.232C>T	p.Pro78Ser	missense_variant	3/4	2	NM_139162.4	ENSP00000323591.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 13, 2023

The c.265C>T (p.P89S) alteration is located in exon 3 (coding exon 3) of the MIEF2 gene. This alteration results from a C to T substitution at nucleotide position 265, causing the proline (P) at amino acid position 89 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T;.;.;T;T;T;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.36	N
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.071	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;L;.;.;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.0	D;.;D;D;.;.;D
REVEL	Benign	0.065
Sift	Benign	0.24	T;.;T;T;.;.;T
Sift4G	Benign	0.28	T;T;T;T;T;T;T
Polyphen		0.052	B;.;B;B;.;.;.
Vest4		0.15
MutPred		0.22		Gain of phosphorylation at P78 (P = 0.0512);Gain of phosphorylation at P78 (P = 0.0512);Gain of phosphorylation at P78 (P = 0.0512);Gain of phosphorylation at P78 (P = 0.0512);Gain of phosphorylation at P78 (P = 0.0512);Gain of phosphorylation at P78 (P = 0.0512);.;
MVP		0.22
MPC		0.34
ClinPred		0.41	T
GERP RS		3.4
Varity_R		0.067
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-18166484;