20-36887791-A-T

Variant names:

• chr20-36887791-A-T
• rs1291139
• NM_080628.3:c.512+263A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080628.3(TLDC2):​c.512+263A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,120 control chromosomes in the GnomAD database, including 44,611 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (44611 hom., cov: 32)
• Consequence: TLDC2 NM_080628.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978
• Publications: 4 publications found

Genes affected

TLDC2 (HGNC:16112): (TBC/LysM-associated domain containing 2) Predicted to be involved in response to oxidative stress. Predicted to act upstream of or within negative regulation of oxidative stress-induced neuron death. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080628.3. 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
	TLDC2	NM_080628.3	MANE Select	c.512+263A>T		intron	N/A	NP_542195.1	A0PJX2
	TLDC2	NM_001304783.1		c.416+263A>T		intron	N/A	NP_001291712.1	A0PJX2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLDC2	ENST00000217320.8	TSL:1 MANE Select	c.512+263A>T		intron	N/A	ENSP00000217320.3	A0PJX2
	TLDC2	ENST00000602922.5	TSL:1	c.512+263A>T		intron	N/A	ENSP00000473323.1	A0PJX2
	TLDC2	ENST00000866646.1		c.512+263A>T		intron	N/A	ENSP00000536705.1

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115080 AN: 152002 Hom.: 44584 Cov.: 32

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.757 AC: 115150 AN: 152120 Hom.: 44611 Cov.: 32 AF XY: 0.754 AC XY: 56075 AN XY: 74382

African (AFR) AF: 0.633 AC: 26238 AN: 41468

American (AMR) AF: 0.676 AC: 10322 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3078 AN: 3472

East Asian (EAS) AF: 0.547 AC: 2827 AN: 5172

South Asian (SAS) AF: 0.836 AC: 4036 AN: 4828

European-Finnish (FIN) AF: 0.759 AC: 8036 AN: 10584

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.853 AC: 58006 AN: 68004

Other (OTH) AF: 0.780 AC: 1646 AN: 2110

Alfa AF: 0.752 Hom.: 2431

Bravo AF: 0.739

Asia WGS AF: 0.696 AC: 2421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.47
DANN	Benign	0.49
PhyloP100		-0.98
PromoterAI		-0.032	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs1291139; hg19: chr20-35516194;