Variant 17-30900495-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_024683.4(TEFM):c.563A>G(p.Lys188Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000339 in 1,614,158 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 3 hom. )

Consequence

TEFM
NM_024683.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.260

Variant links:

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]

TEFM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051493347).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEFM	NM_024683.4 linkuse as main transcript	c.563A>G	p.Lys188Arg	missense_variant	3/4	ENST00000581216.6	NP_078959.3
TEFM	XM_006722084.3 linkuse as main transcript	c.218A>G	p.Lys73Arg	missense_variant	3/4		XP_006722147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEFM	ENST00000581216.6 linkuse as main transcript	c.563A>G	p.Lys188Arg	missense_variant	3/4	1	NM_024683.4	ENSP00000462963	P1	Q96QE5-1
TEFM	ENST00000580840.1 linkuse as main transcript	c.563A>G	p.Lys188Arg	missense_variant	3/3	1		ENSP00000462973
TEFM	ENST00000306049.9 linkuse as main transcript	c.*6A>G		3_prime_UTR_variant, NMD_transcript_variant	3/4	2		ENSP00000306574		Q96QE5-4

Frequencies

GnomAD3 genomes

AF:

0.000328

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000461

AC:

115

AN:

249542

Hom.:

AF XY:

0.000487

AC XY:

AN XY:

135388

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000406

Gnomad ASJ exome

AF:

0.00556

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000265

Gnomad OTH exome

AF:

0.000825

GnomAD4 exome

AF:

0.000343

AC:

501

AN:

1461828

Hom.:

Cov.:

AF XY:

0.000375

AC XY:

273

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00578

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000187

Gnomad4 OTH exome

AF:

0.000878

GnomAD4 genome

AF:

0.000309

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000489

Hom.:

Bravo

AF:

0.000348

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000363

AC:

ExAC

AF:

0.000414

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2022

The c.563A>G (p.K188R) alteration is located in exon 3 (coding exon 3) of the TEFM gene. This alteration results from a A to G substitution at nucleotide position 563, causing the lysine (K) at amino acid position 188 to be replaced by an arginine (R). 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

0.083

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.017

T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.0051

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.33

Sift4G

Benign

0.40

T;T

Polyphen

0.0060

B;.

Vest4

0.19

MVP

0.14

MPC

0.15

ClinPred

0.014

GERP RS

3.5

Varity_R

0.098

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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