chr22-41382195-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003216.4(TEF):c.151C>G(p.Arg51Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000358 in 1,202,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

TEF
NM_003216.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.94

Publications

0 publications found

Variant links:

Genes affected

TEF (HGNC:11722): (TEF transcription factor, PAR bZIP family member) This gene encodes a member of the PAR (proline and acidic amino acid-rich) subfamily of basic region/leucine zipper (bZIP) transcription factors. It is expressed in a broad range of cells and tissues in adult animals, however, during embryonic development, TEF expression appears to be restricted to the developing anterior pituitary gland, coincident with the appearance of thyroid-stimulating hormone, beta (TSHB). Indeed, TEF can bind to, and transactivate the TSHB promoter. It shows homology (in the functional domains) with other members of the PAR-bZIP subfamily of transcription factors, which include albumin D box-binding protein (DBP), human hepatic leukemia factor (HLF) and chicken vitellogenin gene-binding protein (VBP); VBP is considered the chicken homologue of TEF. Different members of the subfamily can readily form heterodimers, and share DNA-binding, and transcriptional regulatory properties. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

TEF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18944347).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEF	NM_003216.4 link	c.151C>G	p.Arg51Gly	missense_variant	Exon 1 of 4	ENST00000266304.9	NP_003207.1	Q10587-1
TEF	NM_001145398.3 link	c.68-5156C>G		intron_variant	Intron 1 of 3		NP_001138870.1	Q10587-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEF	ENST00000266304.9 link	c.151C>G	p.Arg51Gly	missense_variant	Exon 1 of 4	1	NM_003216.4	ENSP00000266304.4		Q10587-1
TEF	ENST00000406644.7 link	c.68-5156C>G		intron_variant	Intron 1 of 3	2		ENSP00000385256.3		Q10587-2

Frequencies

GnomAD3 genomes

AF:

0.0000271

AC:

AN:

147330

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000449

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000370

AC:

AN:

1055458

Hom.:

Cov.:

AF XY:

0.0000461

AC XY:

AN XY:

498586

show subpopulations

African (AFR)

AF:

0.0000454

AC:

AN:

22016

American (AMR)

AF:

0.000123

AC:

AN:

8156

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13002

East Asian (EAS)

AF:

0.00

AC:

AN:

24884

South Asian (SAS)

AF:

0.00

AC:

AN:

19570

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3152

European-Non Finnish (NFE)

AF:

0.0000398

AC:

AN:

903470

Other (OTH)

AF:

0.0000240

AC:

AN:

41622

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000271

AC:

AN:

147330

Hom.:

Cov.:

AF XY:

0.0000279

AC XY:

AN XY:

71788

show subpopulations

African (AFR)

AF:

0.0000251

AC:

AN:

39832

American (AMR)

AF:

0.00

AC:

AN:

14858

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.00

AC:

AN:

4710

South Asian (SAS)

AF:

0.00

AC:

AN:

4452

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9996

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000449

AC:

AN:

66806

Other (OTH)

AF:

0.00

AC:

AN:

2028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 13, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.151C>G (p.R51G) alteration is located in exon 1 (coding exon 1) of the TEF gene. This alteration results from a C to G substitution at nucleotide position 151, causing the arginine (R) at amino acid position 51 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

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.074

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.14

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.020

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.77

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.41

PhyloP100

2.9

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.010

REVEL

Benign

0.089

Sift

Benign

0.40

Sift4G

Benign

0.40

Polyphen

0.0

Vest4

0.14

MutPred

0.38

Loss of helix (P = 0.0167);

MVP

0.27

MPC

1.4

ClinPred

0.66

GERP RS

3.3

PromoterAI

-0.00090

Neutral

(source)

Varity_R

0.18

gMVP

0.22

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr22-41382195-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over