22-41382123-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003216.4(TEF):c.79G>A(p.Gly27Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000171 in 1,235,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

TEF
NM_003216.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.00

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:

LOC105373042 (HGNC:):

LOC105373042 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015569925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEF	NM_003216.4 link	c.79G>A	p.Gly27Arg	missense_variant	Exon 1 of 4	ENST00000266304.9	NP_003207.1	Q10587-1
TEF	NM_001145398.3 link	c.68-5228G>A		intron_variant	Intron 1 of 3		NP_001138870.1	Q10587-2
LOC105373042	XR_938271.3 link	n.-212C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEF	ENST00000266304.9 link	c.79G>A	p.Gly27Arg	missense_variant	Exon 1 of 4	1	NM_003216.4	ENSP00000266304.4		Q10587-1
TEF	ENST00000406644.7 link	c.68-5228G>A		intron_variant	Intron 1 of 3	2		ENSP00000385256.3		Q10587-2

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000204

AC:

AN:

4892

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000303

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000185

AC:

200

AN:

1083094

Hom.:

Cov.:

AF XY:

0.000203

AC XY:

104

AN XY:

511668

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23084

American (AMR)

AF:

0.00

AC:

AN:

8738

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14374

East Asian (EAS)

AF:

0.00

AC:

AN:

26650

South Asian (SAS)

AF:

0.00

AC:

AN:

19706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21230

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3802

European-Non Finnish (NFE)

AF:

0.000209

AC:

193

AN:

921672

Other (OTH)

AF:

0.000160

AC:

AN:

43838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.0000234

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 17, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.79G>A (p.G27R) alteration is located in exon 1 (coding exon 1) of the TEF gene. This alteration results from a G to A substitution at nucleotide position 79, causing the glycine (G) at amino acid position 27 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

0.19

BayesDel_addAF

Uncertain

0.098

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.030

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.60

M_CAP

Pathogenic

0.70

MetaRNN

Benign

0.016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

3.0

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.20

REVEL

Benign

0.096

Sift

Uncertain

0.0060

Sift4G

Benign

0.078

Polyphen

0.36

Vest4

0.21

MutPred

0.23

Gain of helix (P = 0.0117);

MVP

0.41

MPC

2.3

ClinPred

0.74

GERP RS

3.4

PromoterAI

-0.0048

Neutral

(source)

Varity_R

0.18

gMVP

0.34

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

22-41382123-G-A

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