chr22-39517415-C-T

Variant names:

• chr22-39517415-C-T
• rs710192
• NM_019008.6:c.*3092C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019008.6(MIEF1):​c.*3092C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 315,248 control chromosomes in the GnomAD database, including 13,389 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 0.30 (6853 hom., cov: 32)
  • Exomes 𝑓: 0.27 (6536 hom.)
• Consequence: MIEF1 NM_019008.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIEF1	NM_019008.6	c.*3092C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000325301.7	NP_061881.2
MIEF1	NM_001304564.2	c.*2042C>T		3_prime_UTR_variant	Exon 7 of 7		NP_001291493.1
MIEF1	NR_130789.2	n.4885C>T		non_coding_transcript_exon_variant	Exon 6 of 6
MIEF1	NR_130790.2	n.5035C>T		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIEF1	ENST00000325301.7	c.*3092C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_019008.6	ENSP00000327124.2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45198 AN: 151930 Hom.: 6858 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.304

GnomAD4 exome AF: 0.273 AC: 44617 AN: 163200 Hom.: 6536 Cov.: 0 AF XY: 0.279 AC XY: 25481 AN XY: 91434

Gnomad4 AFR exome AF: 0.205

Gnomad4 AMR exome AF: 0.227

Gnomad4 ASJ exome AF: 0.281

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.296

Gnomad4 FIN exome AF: 0.306

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.262

GnomAD4 genome AF: 0.297 AC: 45205 AN: 152048 Hom.: 6853 Cov.: 32 AF XY: 0.296 AC XY: 22026 AN XY: 74298

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.302

Alfa AF: 0.313 Hom.: 12867

Bravo AF: 0.292

Asia WGS AF: 0.314 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	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: rs710192; hg19: chr22-39913420;