22-39513595-G-A

Position:

• chr22-39513595-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_019008.6(MIEF1):​c.664G>A​(p.Asp222Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 1,614,208 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (16 hom.)
• Consequence: MIEF1 NM_019008.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 8.00

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010844678).
• BP6: Variant 22-39513595-G-A is Benign according to our data. Variant chr22-39513595-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2653149.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-39513595-G-A is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd4 at 334 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIEF1	NM_019008.6	c.664G>A	p.Asp222Asn	missense_variant	6/6	ENST00000325301.7	NP_061881.2
MIEF1	NM_001304564.2	c.664G>A	p.Asp222Asn	missense_variant	6/7		NP_001291493.1
MIEF1	NR_130789.2	n.1065G>A		non_coding_transcript_exon_variant	6/6
MIEF1	NR_130790.2	n.1215G>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.664G>A	p.Asp222Asn	missense_variant	6/6	1	NM_019008.6	ENSP00000327124.2

Frequencies

GnomAD3 genomes AF: 0.00219 AC: 334 AN: 152202 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00340

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00257 AC: 646 AN: 251482 Hom.: 2 AF XY: 0.00281 AC XY: 382 AN XY: 135916

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00496

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00604

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00299

Gnomad OTH exome AF: 0.00195

GnomAD4 exome AF: 0.00293 AC: 4284 AN: 1461888 Hom.: 16 Cov.: 31 AF XY: 0.00311 AC XY: 2261 AN XY: 727244

Gnomad4 AFR exome AF: 0.000388

Gnomad4 AMR exome AF: 0.00127

Gnomad4 ASJ exome AF: 0.00471

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00632

Gnomad4 FIN exome AF: 0.000318

Gnomad4 NFE exome AF: 0.00301

Gnomad4 OTH exome AF: 0.00232

GnomAD4 genome AF: 0.00219 AC: 334 AN: 152320 Hom.: 1 Cov.: 32 AF XY: 0.00216 AC XY: 161 AN XY: 74500

Gnomad4 AFR AF: 0.000625

Gnomad4 AMR AF: 0.00189

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00393

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00340

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00307 Hom.: 1

Bravo AF: 0.00210

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00302 AC: 26

ExAC AF: 0.00268 AC: 326

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00398

EpiControl AF: 0.00415

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinal dystrophy Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Jan 01, 2023

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

MIEF1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.053	T;T;T
Eigen	Uncertain	0.58
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;.;D
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.011	T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.4	.;M;M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Benign	0.18
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		0.68	P;P;P
Vest4		0.65
MVP		0.61
MPC		0.52
ClinPred		0.035	T
GERP RS		6.1
Varity_R		0.69
gMVP		0.65

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

LitVar

Other links and lift over

dbSNP: rs138446352; hg19: chr22-39909600;