rs747543160

Variant names:

• chr22-41382121-C-G
• rs747543160
• NM_003216.4:c.77C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-41382121-C-G
• chr22-41382121-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003216.4(TEF):​c.77C>G​(p.Ala26Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000924 in 1,082,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A26V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: TEF NM_003216.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83
• Publications: 0 publications found

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]

LOC105373042 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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>G	p.Ala26Gly	missense	Exon 1 of 4	NP_003207.1	Q10587-1
	TEF	NM_001145398.3		c.68-5230C>G		intron	N/A	NP_001138870.1	Q10587-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEF	ENST00000266304.9	TSL:1 MANE Select	c.77C>G	p.Ala26Gly	missense	Exon 1 of 4	ENSP00000266304.4	Q10587-1
	TEF	ENST00000958295.1		c.77C>G	p.Ala26Gly	missense	Exon 1 of 4	ENSP00000628354.1
	TEF	ENST00000406644.7	TSL:2	c.68-5230C>G		intron	N/A	ENSP00000385256.3	Q10587-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.24e-7 AC: 1 AN: 1082736 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 511462

African (AFR) AF: 0.0000434 AC: 1 AN: 23064

American (AMR) AF: 0.00 AC: 0 AN: 8680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14370

East Asian (EAS) AF: 0.00 AC: 0 AN: 26632

South Asian (SAS) AF: 0.00 AC: 0 AN: 19684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3800

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 921460

Other (OTH) AF: 0.00 AC: 0 AN: 43822

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.52	T
M_CAP	Pathogenic	0.57	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.8
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.41	N
REVEL	Benign	0.087
Sift	Benign	0.040	D
Sift4G	Benign	0.30	T
Polyphen		0.030	B
Vest4		0.12
MutPred		0.17		Loss of helix (P = 0.0237)
MVP		0.26
MPC		1.4
ClinPred		0.53	D
GERP RS		3.3
PromoterAI		0.091	Neutral
Varity_R		0.12
gMVP		0.16
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.73		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.73		Position offset: -1

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

Other links and lift over

dbSNP: rs747543160; hg19: chr22-41778125;