Variant chr16-28843999-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000313511.8(TUFM):c.1025T>G(p.Val342Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

TUFM
ENST00000313511.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.00

Variant links:

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 links:

TUFM (HGNC:):

TUFM links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUFM	NM_003321.5 linkuse as main transcript	c.1025T>G	p.Val342Gly	missense_variant	8/10	ENST00000313511.8	NP_003312.3	P49411A0A384ME17
TUFM	NM_001365360.2 linkuse as main transcript	c.941T>G	p.Val314Gly	missense_variant	8/10		NP_001352289.1
MIR4721	NR_039872.1 linkuse as main transcript	n.9T>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUFM	ENST00000313511.8 linkuse as main transcript	c.1025T>G	p.Val342Gly	missense_variant	8/10	1	NM_003321.5	ENSP00000322439.3		P49411

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250612

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135684

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.1025T>G (p.V342G) alteration is located in exon 8 (coding exon 8) of the TUFM gene. This alteration results from a T to G substitution at nucleotide position 1025, causing the valine (V) at amino acid position 342 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.34

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.98

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

M_CAP

Pathogenic

0.33

MetaRNN

Pathogenic

0.87

MetaSVM

Uncertain

0.47

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-6.3

REVEL

Pathogenic

0.67

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.63

MVP

0.90

MPC

1.8

ClinPred

1.0

GERP RS

6.2

gMVP

0.99

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over