22-41382139-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_003216.4(TEF):c.95C>T(p.Ser32Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,236,160 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

TEF
NM_003216.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35

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: Uncertain_significance. The variant received 2 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity TEF_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15860415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEF	NM_003216.4 link	c.95C>T	p.Ser32Leu	missense_variant	Exon 1 of 4	ENST00000266304.9	NP_003207.1	Q10587-1
TEF	NM_001145398.3 link	c.68-5212C>T		intron_variant	Intron 1 of 3		NP_001138870.1	Q10587-2
LOC105373042	XR_938271.3 link	n.-228G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEF	ENST00000266304.9 link	c.95C>T	p.Ser32Leu	missense_variant	Exon 1 of 4	1	NM_003216.4	ENSP00000266304.4		Q10587-1
TEF	ENST00000406644.7 link	c.68-5212C>T		intron_variant	Intron 1 of 3	2		ENSP00000385256.3		Q10587-2

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1084988

Hom.:

Cov.:

AF XY:

0.00000975

AC XY:

AN XY:

513026

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23156

American (AMR)

AF:

0.00

AC:

AN:

9194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14318

East Asian (EAS)

AF:

0.00

AC:

AN:

26748

South Asian (SAS)

AF:

0.00

AC:

AN:

19886

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3818

European-Non Finnish (NFE)

AF:

0.0000119

AC:

AN:

922786

Other (OTH)

AF:

0.0000228

AC:

AN:

43856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151172

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73856

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41200

American (AMR)

AF:

0.00

AC:

AN:

15198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5052

South Asian (SAS)

AF:

0.00

AC:

AN:

4728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10460

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67772

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 18, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.95C>T (p.S32L) alteration is located in exon 1 (coding exon 1) of the TEF gene. This alteration results from a C to T substitution at nucleotide position 95, causing the serine (S) at amino acid position 32 to be replaced by a leucine (L). 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

Benign

-0.0082

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Benign

-0.11

Eigen_PC

Benign

0.041

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.71

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

1.4

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.56

REVEL

Benign

0.071

Sift

Benign

0.074

Sift4G

Benign

0.31

Polyphen

0.41

Vest4

0.20

MutPred

0.27

Loss of phosphorylation at S32 (P = 0.0136);

MVP

0.18

MPC

0.93

ClinPred

0.87

GERP RS

4.4

PromoterAI

0.034

Neutral

(source)

Varity_R

0.18

gMVP

0.17

Mutation Taster

=77/23

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.

22-41382139-C-T

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