rs1048310

chr22-39517277-T-G

Variant summary

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

The NM_019008.6(MIEF1):c.*2954T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 197,370 control chromosomes in the GnomAD database, including 9,181 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 0.31 (7678 hom., cov: 33)
  • Exomes 𝑓: 0.24 (1503 hom.)
• Consequence: MIEF1 NM_019008.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

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=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIEF1	NM_019008.6	c.*2954T>G		3_prime_UTR_variant	6/6	ENST00000325301.7
MIEF1	NM_001304564.2	c.*1904T>G		3_prime_UTR_variant	7/7
MIEF1	NR_130789.2	n.4747T>G		non_coding_transcript_exon_variant	6/6
MIEF1	NR_130790.2	n.4897T>G		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIEF1	ENST00000325301.7	c.*2954T>G		3_prime_UTR_variant	6/6	1	NM_019008.6	P1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47798 AN: 151994 Hom.: 7679 Cov.: 33

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.316

GnomAD4 exome AF: 0.237 AC: 10747 AN: 45258 Hom.: 1503 Cov.: 0 AF XY: 0.242 AC XY: 6040 AN XY: 24960

Gnomad4 AFR exome AF: 0.226

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.277

Gnomad4 EAS exome AF: 0.130

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.262

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.231

GnomAD4 genome AF: 0.314 AC: 47820 AN: 152112 Hom.: 7678 Cov.: 33 AF XY: 0.314 AC XY: 23316 AN XY: 74348

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.315

Alfa AF: 0.320 Hom.: 7355

Bravo AF: 0.312

Asia WGS AF: 0.322 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	6.0
Dann	Benign	0.78

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: rs1048310; hg19: chr22-39913282; COSMIC: COSV57479002; COSMIC: COSV57479002;