17-30904148-G-C

Position:

• chr17-30904148-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024683.4(TEFM):​c.413C>G​(p.Thr138Ser) variant causes a missense 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TEFM NM_024683.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.954

Genes affected

TEFM (HGNC:26223): (transcription elongation factor, mitochondrial) Enables DNA polymerase processivity factor activity. Involved in mitochondrial transcription and oxidative phosphorylation. Located in mitochondrial nucleoid. Part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052596837).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEFM	NM_024683.4	c.413C>G	p.Thr138Ser	missense_variant	2/4	ENST00000581216.6	NP_078959.3
TEFM	XM_006722084.3	c.68C>G	p.Thr23Ser	missense_variant	2/4		XP_006722147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEFM	ENST00000581216.6	c.413C>G	p.Thr138Ser	missense_variant	2/4	1	NM_024683.4	ENSP00000462963	P1
TEFM	ENST00000580840.1	c.413C>G	p.Thr138Ser	missense_variant	2/3	1		ENSP00000462973
TEFM	ENST00000541382.2	n.450C>G		non_coding_transcript_exon_variant	2/2	2
TEFM	ENST00000306049.9	c.413C>G	p.Thr138Ser	missense_variant, NMD_transcript_variant	2/4	2		ENSP00000306574

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2024

The c.413C>G (p.T138S) alteration is located in exon 2 (coding exon 2) of the TEFM gene. This alteration results from a C to G substitution at nucleotide position 413, causing the threonine (T) at amino acid position 138 to be replaced by a serine (S). 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
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.4
DANN	Benign	0.49
DEOGEN2	Benign	0.0071	T;T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.37	T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.053	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.34	T
Sift4G	Benign	0.46	T;T
Polyphen		0.0060	B;.
Vest4		0.050
MutPred		0.11		Gain of relative solvent accessibility (P = 0.0522);Gain of relative solvent accessibility (P = 0.0522);
MVP		0.18
MPC		0.17
ClinPred		0.021	T
GERP RS		2.5
Varity_R		0.023
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-29231166;