20-36879123-A-T

Variant names:

• chr20-36879123-A-T
• rs754966314
• NM_080628.3:c.272A>T

Variant summary

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

The NM_080628.3(TLDC2):​c.272A>T​(p.Gln91Leu) 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: 32)
• Consequence: TLDC2 NM_080628.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.190
• Publications: 0 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: 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=0.18578869).

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.272A>T	p.Gln91Leu	missense	Exon 3 of 7	NP_542195.1	A0PJX2
	TLDC2	NM_001304783.1		c.272A>T	p.Gln91Leu	missense	Exon 3 of 6	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.272A>T	p.Gln91Leu	missense	Exon 3 of 7	ENSP00000217320.3	A0PJX2
	TLDC2	ENST00000602922.5	TSL:1	c.272A>T	p.Gln91Leu	missense	Exon 3 of 6	ENSP00000473323.1	A0PJX2
	TLDC2	ENST00000866646.1		c.272A>T	p.Gln91Leu	missense	Exon 3 of 7	ENSP00000536705.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

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	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.15	N
PhyloP100		0.19
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.058
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.085	T
Polyphen		0.0080	B
Vest4		0.31
MutPred		0.56		Loss of disorder (P = 0.074)
MVP		0.13
MPC		0.063
ClinPred		0.52	D
GERP RS		-1.9
Varity_R		0.36
gMVP		0.35
Mutation Taster		=78/22	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: rs754966314; hg19: chr20-35507526;