22-39511946-G-A

Variant summary

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

The NM_019008.6(MIEF1):c.242G>A(p.Arg81Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MIEF1 NM_019008.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.15

Genes affected

MIEF1 (HGNC:25979): (mitochondrial elongation factor 1) Enables ADP binding activity; GDP binding activity; and identical protein binding activity. Involved in several processes, including positive regulation of mitochondrial fission; positive regulation of mitochondrial translation; and positive regulation of protein targeting to membrane. Located in mitochondrial matrix and mitochondrial outer membrane. Colocalizes with mitochondrial large ribosomal subunit. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIEF1	NM_019008.6	c.242G>A	p.Arg81Gln	missense_variant	4/6	ENST00000325301.7
MIEF1	NM_001304564.2	c.242G>A	p.Arg81Gln	missense_variant	4/7
MIEF1	NR_130789.2	n.729G>A		non_coding_transcript_exon_variant	4/6
MIEF1	NR_130790.2	n.879G>A		non_coding_transcript_exon_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIEF1	ENST00000325301.7	c.242G>A	p.Arg81Gln	missense_variant	4/6	1	NM_019008.6	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461846 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

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

May 04, 2022

The c.242G>A (p.R81Q) alteration is located in exon 4 (coding exon 2) of the MIEF1 gene. This alteration results from a G to A substitution at nucleotide position 242, causing the arginine (R) at amino acid position 81 to be replaced by a glutamine (Q). 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	0.13
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
Cadd	Uncertain	25
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.046	T;T;T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.73	T;.;T
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.62	N;N;N
REVEL	Benign	0.19
Sift	Benign	0.078	T;T;T
Sift4G	Benign	0.19	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.47
MutPred		0.26		Loss of MoRF binding (P = 0.0107);Loss of MoRF binding (P = 0.0107);Loss of MoRF binding (P = 0.0107);
MVP		0.59
MPC		1.2
ClinPred		0.85	D
GERP RS		4.9
Varity_R		0.037
gMVP		0.34

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: chr22-39907951;