chr20-36879188-G-T

Variant names:

• chr20-36879188-G-T
• rs202081152
• NM_080628.3:c.337G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_080628.3(TLDC2):​c.337G>T​(p.Gly113Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. G113E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TLDC2 NM_080628.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.00
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.818

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.337G>T	p.Gly113Trp	missense	Exon 3 of 7	NP_542195.1	A0PJX2
	TLDC2	NM_001304783.1		c.337G>T	p.Gly113Trp	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.337G>T	p.Gly113Trp	missense	Exon 3 of 7	ENSP00000217320.3	A0PJX2
	TLDC2	ENST00000602922.5	TSL:1	c.337G>T	p.Gly113Trp	missense	Exon 3 of 6	ENSP00000473323.1	A0PJX2
	TLDC2	ENST00000866646.1		c.337G>T	p.Gly113Trp	missense	Exon 3 of 7	ENSP00000536705.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459970 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726272

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111502

Other (OTH) AF: 0.00 AC: 0 AN: 60342

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.33	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		5.0
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.93	P
Vest4		0.57
MutPred		0.67		Loss of disorder (P = 0.0857)
MVP		0.64
MPC		0.36
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.77
gMVP		0.54
Mutation Taster		=58/42	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: rs202081152; hg19: chr20-35507591;