chr22-41382121-C-T

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.77C>T(p.Ala26Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,234,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

TEF
NM_003216.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.83

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:

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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=0.20845461).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003216.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEF	NM_003216.4	MANE Select	c.77C>T	p.Ala26Val	missense	Exon 1 of 4	NP_003207.1	Q10587-1
	TEF	NM_001145398.3		c.68-5230C>T		intron	N/A	NP_001138870.1	Q10587-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TEF	ENST00000266304.9	TSL:1 MANE Select	c.77C>T	p.Ala26Val	missense	Exon 1 of 4	ENSP00000266304.4	Q10587-1
TEF	ENST00000958295.1		c.77C>T	p.Ala26Val	missense	Exon 1 of 4	ENSP00000628354.1
TEF	ENST00000406644.7	TSL:2	c.68-5230C>T		intron	N/A	ENSP00000385256.3	Q10587-2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151754

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

4502

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000554

AC:

AN:

1082736

Hom.:

Cov.:

AF XY:

0.0000704

AC XY:

AN XY:

511462

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23064

American (AMR)

AF:

0.00

AC:

AN:

8680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14370

East Asian (EAS)

AF:

0.00

AC:

AN:

26632

South Asian (SAS)

AF:

0.00

AC:

AN:

19684

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21224

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3800

European-Non Finnish (NFE)

AF:

0.0000629

AC:

AN:

921460

Other (OTH)

AF:

0.0000456

AC:

AN:

43822

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151754

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74122

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000242

AC:

AN:

41316

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67866

Other (OTH)

AF:

0.00

AC:

AN:

2084

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000118

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.59

M_CAP

Pathogenic

0.59

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

2.8

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.60

REVEL

Benign

0.069

Sift

Uncertain

0.022

Sift4G

Benign

0.67

Polyphen

0.0

Vest4

0.21

MutPred

0.21

Loss of helix (P = 0.0376)

MVP

0.26

MPC

1.6

ClinPred

0.78

GERP RS

3.3

PromoterAI

0.045

Neutral

(source)

Varity_R

0.15

gMVP

0.26

Mutation Taster

=93/7

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over