16-28842705-G-C

Variant names:

• chr16-28842705-G-C
• rs867305584
• NM_003321.5:c.*270C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003321.5(TUFM):​c.*270C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: TUFM NM_003321.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387
• Publications: 0 publications found

Genes affected

TUFM (HGNC:12420): (Tu translation elongation factor, mitochondrial) This gene encodes a protein which participates in protein translation in mitochondria. Mutations in this gene have been associated with combined oxidative phosphorylation deficiency resulting in lactic acidosis and fatal encephalopathy. A pseudogene has been identified on chromosome 17. [provided by RefSeq, Jul 2008]

TUFM Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation defect type 4

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003321.5. 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
	TUFM	NM_003321.5	MANE Select	c.*270C>G		3_prime_UTR	Exon 10 of 10	NP_003312.3
	TUFM	NM_001365360.2		c.*270C>G		3_prime_UTR	Exon 10 of 10	NP_001352289.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUFM	ENST00000313511.8	TSL:1 MANE Select	c.*270C>G		3_prime_UTR	Exon 10 of 10	ENSP00000322439.3	P49411
	TUFM	ENST00000916488.1		c.*270C>G		3_prime_UTR	Exon 10 of 10	ENSP00000586547.1
	TUFM	ENST00000916490.1		c.*270C>G		downstream_gene	N/A	ENSP00000586549.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 2

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.5
DANN	Benign	0.85
PhyloP100		0.39

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: rs867305584; hg19: chr16-28854026;