19-3062727-C-G

Position:

• chr19-3062727-C-G

Variant summary

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

The NM_198969.1(TLE5):​c.201G>C​(p.Trp67Cys) 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. 10/17 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: TLE5 NM_198969.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0160

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]

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=0.17111129).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLE5	NM_198969.1	c.201G>C	p.Trp67Cys	missense_variant	1/7		NP_945320.1
TLE5	XM_006722664.2	c.201G>C	p.Trp67Cys	missense_variant	1/7		XP_006722727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLE5	ENST00000221561.12	c.201G>C	p.Trp67Cys	missense_variant	1/7	1		ENSP00000221561.7
TLE5	ENST00000586742.5	c.156G>C	p.Trp52Cys	missense_variant	1/6	3		ENSP00000466038.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.201G>C (p.W67C) alteration is located in exon 1 (coding exon 1) of the AES gene. This alteration results from a G to C substitution at nucleotide position 201, causing the tryptophan (W) at amino acid position 67 to be replaced by a cysteine (C). 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
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.50
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.53	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.058
Sift	Benign	0.081	T
Sift4G	Benign	0.23	T
Vest4		0.17
MutPred		0.46		Loss of MoRF binding (P = 0.0104);
MVP		0.53
MPC		2.2
ClinPred		0.11	T
GERP RS		0.50
gMVP		0.048

Splicing

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: chr19-3062725;