rs769059682

Variant names:

• chr22-39512339-C-G
• NM_019008.6:c.430C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-39512339-C-G
• chr22-39512339-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019008.6(MIEF1):​c.430C>G​(p.Arg144Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R144P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MIEF1 NM_019008.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.82

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36924988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIEF1	NM_019008.6	c.430C>G	p.Arg144Gly	missense_variant	Exon 5 of 6	ENST00000325301.7	NP_061881.2
MIEF1	NM_001304564.2	c.430C>G	p.Arg144Gly	missense_variant	Exon 5 of 7		NP_001291493.1
MIEF1	NR_130789.2	n.831C>G		non_coding_transcript_exon_variant	Exon 5 of 6
MIEF1	NR_130790.2	n.981C>G		non_coding_transcript_exon_variant	Exon 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIEF1	ENST00000325301.7	c.430C>G	p.Arg144Gly	missense_variant	Exon 5 of 6	1	NM_019008.6	ENSP00000327124.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461866 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.048	T;T;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T;.;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	.;M;M
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Benign	0.098
Sift	Uncertain	0.029	D;D;D
Sift4G	Uncertain	0.046	D;T;T
Polyphen		0.72	P;B;B
Vest4		0.68
MutPred		0.29		Loss of MoRF binding (P = 0.0436);Loss of MoRF binding (P = 0.0436);Loss of MoRF binding (P = 0.0436);
MVP		0.32
MPC		0.61
ClinPred		0.83	D
GERP RS		5.8
Varity_R		0.69
gMVP		0.26

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: chr22-39908344;