rs143713547

Variant names:

• chr19-3000657-C-T
• rs143713547
• NM_003260.5:c.2114G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-3000657-C-T
• chr19-3000657-C-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003260.5(TLE2):​c.2114G>A​(p.Ser705Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0049 in 1,587,666 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0084 (6 hom., cov: 30)
  • Exomes 𝑓: 0.0045 (39 hom.)
• Consequence: TLE2 NM_003260.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 7.84
• Publications: 10 publications found

Genes affected

TLE2 (HGNC:11838): (TLE family member 2, transcriptional corepressor) Enables transcription corepressor activity. Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of transcription, DNA-templated. Located in focal adhesion and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009703219).
• BP6: Variant 19-3000657-C-T is Benign according to our data. Variant chr19-3000657-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1679860.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00453 (6507/1435534) while in subpopulation MID AF = 0.0346 (195/5642). AF 95% confidence interval is 0.0306. There are 39 homozygotes in GnomAdExome4. There are 3226 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003260.5. 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
	TLE2	NM_003260.5	MANE Select	c.2114G>A	p.Ser705Asn	missense	Exon 19 of 20	NP_003251.2
	TLE2	NM_001300846.2		c.2117G>A	p.Ser706Asn	missense	Exon 19 of 20	NP_001287775.1	K7EMK7
	TLE2	NM_001144762.2		c.1748G>A	p.Ser583Asn	missense	Exon 17 of 18	NP_001138234.1	Q04725-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLE2	ENST00000262953.11	TSL:1 MANE Select	c.2114G>A	p.Ser705Asn	missense	Exon 19 of 20	ENSP00000262953.5	Q04725-1
	TLE2	ENST00000590536.5	TSL:1	c.2117G>A	p.Ser706Asn	missense	Exon 19 of 20	ENSP00000466542.1	K7EMK7
	TLE2	ENST00000591529.5	TSL:1	c.2089+1696G>A		intron	N/A	ENSP00000468279.1	Q04725-3

Frequencies

GnomAD3 genomes AF: 0.00835 AC: 1270 AN: 152014 Hom.: 6 Cov.: 30

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00985

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.00454

Gnomad OTH AF: 0.0149

GnomAD2 exomes AF: 0.00553 AC: 1156 AN: 208862 AF XY: 0.00517

Gnomad AFR exome AF: 0.0128

Gnomad AMR exome AF: 0.00697

Gnomad ASJ exome AF: 0.00776

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00972

Gnomad NFE exome AF: 0.00492

Gnomad OTH exome AF: 0.00845

GnomAD4 exome AF: 0.00453 AC: 6507 AN: 1435534 Hom.: 39 Cov.: 31 AF XY: 0.00453 AC XY: 3226 AN XY: 711546

African (AFR) AF: 0.0140 AC: 459 AN: 32798

American (AMR) AF: 0.00724 AC: 296 AN: 40862

Ashkenazi Jewish (ASJ) AF: 0.00710 AC: 182 AN: 25640

East Asian (EAS) AF: 0.00 AC: 0 AN: 38252

South Asian (SAS) AF: 0.00224 AC: 184 AN: 82040

European-Finnish (FIN) AF: 0.00932 AC: 479 AN: 51388

Middle Eastern (MID) AF: 0.0346 AC: 195 AN: 5642

European-Non Finnish (NFE) AF: 0.00387 AC: 4255 AN: 1099434

Other (OTH) AF: 0.00768 AC: 457 AN: 59478

GnomAD4 genome AF: 0.00836 AC: 1272 AN: 152132 Hom.: 6 Cov.: 30 AF XY: 0.00832 AC XY: 619 AN XY: 74382

African (AFR) AF: 0.0149 AC: 619 AN: 41536

American (AMR) AF: 0.00983 AC: 150 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4814

European-Finnish (FIN) AF: 0.0107 AC: 113 AN: 10600

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.00453 AC: 308 AN: 67994

Other (OTH) AF: 0.0147 AC: 31 AN: 2106

Alfa AF: 0.00591 Hom.: 15

Bravo AF: 0.00860

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.0127 AC: 50

ESP6500EA AF: 0.00399 AC: 33

ExAC AF: 0.00509 AC: 613

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Decreased total lymphocyte count;C0853697:Decreased total neutrophil count (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.54
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.0097	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.7	L
PhyloP100		7.8
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.20
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.046	D
Polyphen		0.97	D
Vest4		0.75
MVP		0.73
MPC		0.92
ClinPred		0.023	T
GERP RS		4.0
Varity_R		0.58
gMVP		0.60
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs143713547; hg19: chr19-3000655;