22-41382081-G-A

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.37G>A(p.Asp13Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000185 in 1,079,696 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: not found (cov: 33)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

TEF
NM_003216.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47

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=0.11187345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEF	NM_003216.4 link	c.37G>A	p.Asp13Asn	missense_variant	Exon 1 of 4	ENST00000266304.9	NP_003207.1	Q10587-1
TEF	NM_001145398.3 link	c.68-5270G>A		intron_variant	Intron 1 of 3		NP_001138870.1	Q10587-2
LOC105373042	XR_938271.3 link	n.-170C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEF	ENST00000266304.9 link	c.37G>A	p.Asp13Asn	missense_variant	Exon 1 of 4	1	NM_003216.4	ENSP00000266304.4		Q10587-1
TEF	ENST00000406644.7 link	c.68-5270G>A		intron_variant	Intron 1 of 3	2		ENSP00000385256.3		Q10587-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000185

AC:

AN:

1079696

Hom.:

Cov.:

AF XY:

0.00000392

AC XY:

AN XY:

509712

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22962

American (AMR)

AF:

0.00

AC:

AN:

8406

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14348

East Asian (EAS)

AF:

0.00

AC:

AN:

26516

South Asian (SAS)

AF:

0.00

AC:

AN:

19542

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21108

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3298

European-Non Finnish (NFE)

AF:

0.00000217

AC:

AN:

919842

Other (OTH)

AF:

0.00

AC:

AN:

43674

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 25, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.37G>A (p.D13N) 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 37, causing the aspartic acid (D) at amino acid position 13 to be replaced by an asparagine (N). 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

0.15

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.45

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

3.5

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

0.18

REVEL

Benign

0.17

Sift

Benign

0.072

Sift4G

Benign

0.11

Polyphen

0.0

Vest4

0.14

MutPred

0.10

Gain of glycosylation at P11 (P = 0.0974);

MVP

0.12

MPC

0.99

ClinPred

0.53

GERP RS

4.3

PromoterAI

0.0055

Neutral

(source)

Varity_R

0.19

gMVP

0.19

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over