rs3088215

Variant names:

• chr16-28842675-A-C
• rs3088215
• NM_003321.5:c.*300T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003321.5(TUFM):​c.*300T>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 0.343 in 438,128 control chromosomes in the GnomAD database, including 27,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9551 hom., cov: 32)
  • Exomes 𝑓: 0.34 (18289 hom.)
• Consequence: TUFM NM_003321.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.57
• Publications: 26 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-28842675-A-C is Benign according to our data. Variant chr16-28842675-A-C is described in ClinVar as Benign. ClinVar VariationId is 318738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

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.*300T>G		3_prime_UTR	Exon 10 of 10	NP_003312.3
	TUFM	NM_001365360.2		c.*300T>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.*300T>G		3_prime_UTR	Exon 10 of 10	ENSP00000322439.3	P49411
	TUFM	ENST00000916488.1		c.*300T>G		3_prime_UTR	Exon 10 of 10	ENSP00000586547.1
	TUFM	ENST00000916490.1		c.*300T>G		downstream_gene	N/A	ENSP00000586549.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51873 AN: 151980 Hom.: 9522 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.305

GnomAD4 exome AF: 0.344 AC: 98372 AN: 286030 Hom.: 18289 Cov.: 0 AF XY: 0.333 AC XY: 50768 AN XY: 152444

African (AFR) AF: 0.261 AC: 2215 AN: 8500

American (AMR) AF: 0.452 AC: 5897 AN: 13038

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 2213 AN: 8184

East Asian (EAS) AF: 0.122 AC: 1922 AN: 15736

South Asian (SAS) AF: 0.225 AC: 9496 AN: 42220

European-Finnish (FIN) AF: 0.420 AC: 6241 AN: 14870

Middle Eastern (MID) AF: 0.219 AC: 250 AN: 1140

European-Non Finnish (NFE) AF: 0.389 AC: 64749 AN: 166650

Other (OTH) AF: 0.343 AC: 5389 AN: 15692

GnomAD4 genome AF: 0.342 AC: 51966 AN: 152098 Hom.: 9551 Cov.: 32 AF XY: 0.340 AC XY: 25258 AN XY: 74326

African (AFR) AF: 0.267 AC: 11058 AN: 41490

American (AMR) AF: 0.406 AC: 6207 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 928 AN: 3470

East Asian (EAS) AF: 0.121 AC: 629 AN: 5180

South Asian (SAS) AF: 0.217 AC: 1048 AN: 4826

European-Finnish (FIN) AF: 0.423 AC: 4463 AN: 10562

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26691 AN: 67980

Other (OTH) AF: 0.309 AC: 653 AN: 2112

Alfa AF: 0.372 Hom.: 1460

Bravo AF: 0.339

Asia WGS AF: 0.275 AC: 952 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Combined oxidative phosphorylation defect type 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.83
DANN	Benign	0.67
PhyloP100		-1.6
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: rs3088215; hg19: chr16-28853996;