chr22-39511656-G-C

Variant names:

• chr22-39511656-G-C
• rs738288
• NM_019008.6:c.145-193G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019008.6(MIEF1):​c.145-193G>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: 34)
• Consequence: MIEF1 NM_019008.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• Publications: 18 publications found

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]

MIEF1 Gene-Disease associations (from GenCC):

• optic atrophy 14

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIEF1	NM_019008.6	c.145-193G>C		intron_variant	Intron 3 of 5	ENST00000325301.7	NP_061881.2
MIEF1	NM_001304564.2	c.145-193G>C		intron_variant	Intron 3 of 6		NP_001291493.1
MIEF1	NR_130789.2	n.632-193G>C		intron_variant	Intron 3 of 5
MIEF1	NR_130790.2	n.782-193G>C		intron_variant	Intron 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIEF1	ENST00000325301.7	c.145-193G>C		intron_variant	Intron 3 of 5	1	NM_019008.6	ENSP00000327124.2

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.66
DANN	Benign	0.56
PhyloP100		-0.49

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: rs738288; hg19: chr22-39907661;