rs779912568

Variant names:

• chr9-79706828-G-A
• NM_007005.6:c.865G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-79706828-G-A
• chr9-79706828-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007005.6(TLE4):​c.865G>A​(p.Ala289Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,886 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. A289P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TLE4 NM_007005.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.62

Genes affected

TLE4 (HGNC:11840): (TLE family member 4, transcriptional corepressor) Predicted to enable transcription corepressor activity. Predicted to be involved in negative regulation of canonical Wnt signaling pathway. Predicted to act upstream of or within Wnt signaling pathway; cellular response to leukemia inhibitory factor; and negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19934198).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLE4	NM_007005.6	c.865G>A	p.Ala289Thr	missense_variant	Exon 11 of 20	ENST00000376552.8	NP_008936.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLE4	ENST00000376552.8	c.865G>A	p.Ala289Thr	missense_variant	Exon 11 of 20	1	NM_007005.6	ENSP00000365735.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;.;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.8	L;L;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.51	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.23
MutPred		0.22		Gain of phosphorylation at A289 (P = 0.0189);Gain of phosphorylation at A289 (P = 0.0189);.;
MVP		0.082
MPC		0.34
ClinPred		0.83	D
GERP RS		5.9
Varity_R		0.088
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-82321743;