19-3053962-G-A

Variant names:

• chr19-3053962-G-A
• NM_001130.6:c.451C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001130.6(TLE5):​c.451C>T​(p.Pro151Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TLE5 NM_001130.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.43

Genes affected

TLE5 (HGNC:307): (TLE family member 5, transcriptional modulator) The protein encoded by this gene is similar in sequence to the amino terminus of Drosophila enhancer of split groucho, a protein involved in neurogenesis during embryonic development. The encoded protein, which belongs to the groucho/TLE family of proteins, can function as a homooligomer or as a heteroologimer with other family members to dominantly repress the expression of other family member genes. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000267469 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26620287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLE5	NM_001130.6	c.451C>T	p.Pro151Ser	missense_variant	Exon 7 of 7	ENST00000327141.9	NP_001121.2
TLE5	NM_198969.1	c.652C>T	p.Pro218Ser	missense_variant	Exon 7 of 7		NP_945320.1
TLE5	NM_198970.2	c.448C>T	p.Pro150Ser	missense_variant	Exon 7 of 7		NP_945321.1
TLE5	XM_006722664.2	c.649C>T	p.Pro217Ser	missense_variant	Exon 7 of 7		XP_006722727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLE5	ENST00000327141.9	c.451C>T	p.Pro151Ser	missense_variant	Exon 7 of 7	1	NM_001130.6	ENSP00000317537.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.652C>T (p.P218S) alteration is located in exon 7 (coding exon 7) of the AES gene. This alteration results from a C to T substitution at nucleotide position 652, causing the proline (P) at amino acid position 218 to be replaced by a serine (S). 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	0.069
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	.;D;.
Eigen	Benign	-0.082
Eigen_PC	Benign	-0.045
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	.;M;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-4.7	D;D;.
REVEL	Benign	0.086
Sift	Uncertain	0.0040	D;D;.
Sift4G	Uncertain	0.040	D;T;T
Polyphen		0.043	.;B;.
Vest4		0.46
MutPred		0.30		.;Loss of catalytic residue at P151 (P = 0.0019);.;
MVP		0.44
MPC		0.41
ClinPred		0.99	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.68

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: chr19-3053960;