rs375697013

Variant names:

• chr19-3053974-C-A
• rs375697013
• NM_001130.6:c.439G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-3053974-C-A
• chr19-3053974-C-G
• chr19-3053974-C-T

Variant summary

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

The NM_001130.6(TLE5):​c.439G>T​(p.Val147Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. V147M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TLE5 NM_001130.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07206321).

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.439G>T	p.Val147Leu	missense	Exon 7 of 7	NP_001121.2
	TLE5	NM_198969.1		c.640G>T	p.Val214Leu	missense	Exon 7 of 7	NP_945320.1	Q08117-2
	TLE5	NM_198970.2		c.436G>T	p.Val146Leu	missense	Exon 7 of 7	NP_945321.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLE5	ENST00000327141.9	TSL:1 MANE Select	c.439G>T	p.Val147Leu	missense	Exon 7 of 7	ENSP00000317537.4	Q08117-1
	TLE5	ENST00000221561.12	TSL:1	c.640G>T	p.Val214Leu	missense	Exon 7 of 7	ENSP00000221561.7	Q08117-2
	TLE5	ENST00000586839.1	TSL:1	c.271G>T	p.Val91Leu	missense	Exon 6 of 6	ENSP00000467831.1	K7EQH5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458028 Hom.: 0 Cov.: 41 AF XY: 0.00 AC XY: 0 AN XY: 725206

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 85974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5346

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110952

Other (OTH) AF: 0.0000166 AC: 1 AN: 60188

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.73	N
PhyloP100		1.3
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.035
Sift	Benign	0.14	T
Sift4G	Benign	0.35	T
Polyphen		0.0010	B
Vest4		0.064
MutPred		0.14		Gain of glycosylation at P146 (P = 0.0637)
MVP		0.28
MPC		0.35
ClinPred		0.18	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.083
gMVP		0.58
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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

dbSNP: rs375697013; hg19: chr19-3053972;