19-2982178-C-A

Variant names:

• chr19-2982178-C-A
• NM_001143986.2:c.211C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001143986.2(TLE6):​c.211C>A​(p.His71Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: TLE6 NM_001143986.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.711
• Publications: 0 publications found

Genes affected

TLE6 (HGNC:30788): (TLE family member 6, subcortical maternal complex member) This gene encodes a member of the Groucho/ transducin-like Enhancer of split family of transcriptional co-repressors. The encoded protein is a component of the mammalian subcortical maternal complex, which is required for preimplantation development. In mouse, knock out of this gene results in cleavage-stage embryonic arrest resulting from defective cytoplasmic F-actin meshwork formation and asymmetric cell division. In human, an allelic variant in this gene is associated with preimplantation embryonic lethality. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

TLE6 Gene-Disease associations (from GenCC):

• preimplantation embryonic lethality 1

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

ACMG classification

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=0.12756628).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143986.2. 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
	TLE6	NM_001143986.2	MANE Select	c.211C>A	p.His71Asn	missense	Exon 5 of 17	NP_001137458.1	Q9H808-1
	TLE6	NM_024760.3		c.-159C>A		5_prime_UTR	Exon 4 of 16	NP_079036.1	Q9H808-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLE6	ENST00000246112.9	TSL:1 MANE Select	c.211C>A	p.His71Asn	missense	Exon 5 of 17	ENSP00000246112.3	Q9H808-1
	TLE6	ENST00000452088.5	TSL:1	c.-159C>A		5_prime_UTR	Exon 4 of 16	ENSP00000406893.1	Q9H808-2
	TLE6	ENST00000958788.1		c.211C>A	p.His71Asn	missense	Exon 5 of 17	ENSP00000628847.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.86
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.71
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.066
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.16	T
Vest4		0.38
MutPred		0.21		Gain of ubiquitination at K73 (P = 0.1008)
MVP		0.56
MPC		0.069
ClinPred		0.34	T
GERP RS		1.4
Varity_R		0.17
gMVP		0.059
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr19-2982176;