Genetic Variant TLDC2:p.Gly113Trp (chr20-36879188-G-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.00

Publications

0 publications found

Variant links:

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]

TLDC2 links:

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ACMG classification

Classification was made for transcript

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

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.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1459970

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726272

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111502

Other (OTH)

AF:

0.00

AC:

AN:

60342

GnomAD4 genome

Cov.:

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

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.85

M_CAP

Benign

0.041

MetaRNN

Pathogenic

0.82

MetaSVM

Benign

-0.33

MutationAssessor

Pathogenic

3.6

PhyloP100

5.0

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-6.3

REVEL

Uncertain

0.31

Sift

Uncertain

0.015

Sift4G

Uncertain

0.0030

Polyphen

0.93

Vest4

0.57

MutPred

0.67

Loss of disorder (P = 0.0857)

MVP

0.64

MPC

0.36

ClinPred

0.99

GERP RS

5.1

Varity_R

0.77

gMVP

0.54

Mutation Taster

=58/42

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over