rs738288

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr22-39511656-G-A
• chr22-39511656-G-C
• chr22-39511656-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019008.6(MIEF1):​c.145-193G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 152,140 control chromosomes in the GnomAD database, including 30,393 homozygotes. 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: 𝑓 0.62 (30393 hom., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019008.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIEF1	NM_019008.6	MANE Select	c.145-193G>A		intron	N/A	NP_061881.2
	MIEF1	NM_001304564.2		c.145-193G>A		intron	N/A	NP_001291493.1	B0QY95
	MIEF1	NR_130789.2		n.632-193G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIEF1	ENST00000325301.7	TSL:1 MANE Select	c.145-193G>A		intron	N/A	ENSP00000327124.2	Q9NQG6-1
	MIEF1	ENST00000402881.5	TSL:1	c.145-193G>A		intron	N/A	ENSP00000385110.1	B0QY95
	MIEF1	ENST00000433117.6	TSL:1	n.145-193G>A		intron	N/A	ENSP00000404096.2	Q9NQG6-2

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94817 AN: 152022 Hom.: 30358 Cov.: 34

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.624 AC: 94896 AN: 152140 Hom.: 30393 Cov.: 34 AF XY: 0.629 AC XY: 46756 AN XY: 74370

African (AFR) AF: 0.715 AC: 29659 AN: 41484

American (AMR) AF: 0.594 AC: 9083 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2213 AN: 3468

East Asian (EAS) AF: 0.991 AC: 5139 AN: 5188

South Asian (SAS) AF: 0.632 AC: 3046 AN: 4818

European-Finnish (FIN) AF: 0.618 AC: 6542 AN: 10580

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 37110 AN: 67992

Other (OTH) AF: 0.651 AC: 1376 AN: 2114

Alfa AF: 0.576 Hom.: 26608

Bravo AF: 0.629

Asia WGS AF: 0.834 AC: 2898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.76
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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;