22-39513649-T-A

Position:

• chr22-39513649-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The ENST00000325301.7(MIEF1):​c.718T>A​(p.Tyr240Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MIEF1 ENST00000325301.7 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.01

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.818
• PP5: Variant 22-39513649-T-A is Pathogenic according to our data. Variant chr22-39513649-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 2626805.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIEF1	NM_019008.6	c.718T>A	p.Tyr240Asn	missense_variant	6/6	ENST00000325301.7	NP_061881.2
MIEF1	NM_001304564.2	c.718T>A	p.Tyr240Asn	missense_variant	6/7		NP_001291493.1
MIEF1	NR_130789.2	n.1119T>A		non_coding_transcript_exon_variant	6/6
MIEF1	NR_130790.2	n.1269T>A		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIEF1	ENST00000325301.7	c.718T>A	p.Tyr240Asn	missense_variant	6/6	1	NM_019008.6	ENSP00000327124	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Optic atrophy 14 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 24, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T;T;T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;.;D
M_CAP	Benign	0.081	D
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.6	.;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-4.7	D;D;D
REVEL	Uncertain	0.41
Sift	Benign	0.073	T;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.95
MutPred		0.53		Gain of disorder (P = 0.0308);Gain of disorder (P = 0.0308);Gain of disorder (P = 0.0308);
MVP		0.50
MPC		1.4
ClinPred		0.99	D
GERP RS		6.1
Varity_R		0.97
gMVP		0.75

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: chr22-39909654;