19-3053972-CAC-GAG

Variant names:

• chr19-3053972-CAC-GAG
• NM_001130.6:c.439_441delGTGinsCTC
• TLE5 p.Val147Leu

Variant summary

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

The NM_001130.6(TLE5):​c.439_441delGTGinsCTC​(p.Val147Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. V147M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TLE5 NM_001130.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130.6. 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
	TLE5	NM_001130.6	MANE Select	c.439_441delGTGinsCTC	p.Val147Leu	missense	N/A	NP_001121.2
	TLE5	NM_198969.1		c.640_642delGTGinsCTC	p.Val214Leu	missense	N/A	NP_945320.1	Q08117-2
	TLE5	NM_198970.2		c.436_438delGTGinsCTC	p.Val146Leu	missense	N/A	NP_945321.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLE5	ENST00000327141.9	TSL:1 MANE Select	c.439_441delGTGinsCTC	p.Val147Leu	missense	N/A	ENSP00000317537.4	Q08117-1
	TLE5	ENST00000221561.12	TSL:1	c.640_642delGTGinsCTC	p.Val214Leu	missense	N/A	ENSP00000221561.7	Q08117-2
	TLE5	ENST00000586839.1	TSL:1	c.271_273delGTGinsCTC	p.Val91Leu	missense	N/A	ENSP00000467831.1	K7EQH5

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-3053970;